Coverage Policies

Use the index below to search for coverage information on specific medical conditions.

High-Tech Imaging: High-Tech Imaging services are administered by National Imaging Associates, Inc. (NIA). For coverage information and authorizations, click here.

Medical Providers: Payment for care or services is based on eligibility, medical necessity and available benefits at time of service and is subject to all contractual exclusions and limitations, including pre-existing conditions if applicable.

Future eligibility cannot be guaranteed and should be rechecked at time of service. Verify benefits by signing into My Account or calling Customer Service at 800.235.7111 or 501.228.7111.

If not specified in a QualChoice coverage policy (Benefit Interpretation), QualChoice follows care guidelines published by MCG Health.

QualChoice reserves the right to alter, amend, change or supplement medical policies as needed. QualChoice reviews and authorizes services and substances. CPT and HCPCS codes are listed as a convenience and any absent, new or changed codes do not alter the intent of the policy.


Effective Date: 02/03/2010 Title: Tumor Markers
Revision Date: 01/01/2020 Document: BI129:00
CPT Code(s): 0002U, 0003U, 0005U, 0009U, 0021U, 0045U, 81313, 81479, 81518, 81519, 81522, 81539, 81551, 81599, 82378, 84152-84154, 84233, 84234, 86294, 86300, 86301, 86304, 86316, 86386
Public Statement

Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

1.    PSA is covered.

2.    Some tumor marker tests require pre-authorization.

3.    Tumor markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign conditions.  These substances can be found in the blood, tumor tissue, or other tissues or bodily fluids of some patients with cancer.

4.    Some tumor markers are substances normally produced in low quantities by cells in the body. Detection of a higher-than-normal serum levels may indicate the presence of a certain type of cancer.  Currently, the main use of such markers is to assess a cancer`s response to treatment and to check for recurrence.

5.    In some types of cancer, tumor marker levels may reflect the extent or stage of the disease and can be useful in predicting how well the disease will respond to treatment. This is especially the case for certain patterns of gene expression and changes to DNA.

6.    CEA, CA125, CA15-3, NMP-22, and CA19-9 are covered for specific diagnoses. All other tumor markers require preauthorization.

7.    CEA is not covered as a screening test.

8.    Percent free PSA is covered with elevated PSA but the 4K score and Prostate Health Index (PHI)—both of which include free PSA—and the ConfirmMDx and PCA3 are not covered. When NCCN guidelines or DNA Direct indicate that multiple testing options exist for the same clinical scenario, we will only cover the test(s) that meet medical necessity criteria (see BI024).

9.    In order to avoid inaccurate, incomplete or untimely requests, all prior-authorization requests for Blood genetic tests require the following:

a) The request is submitted by the ordering provider office, AND

b) Submitted clinical is from patient medical records such as provider clinic progress notes. Information on lab request forms is not accepted, AND the request is submitted before testing and not more than 3 business days after the collection of blood specimen.

Medical Statement

1.  QualChoice considers any of the following serum tumor markers for the stated indication medically necessary:

A.   For prostate cancer screening, staging, monitoring response to therapy, and detecting disease recurrence. 

1)    Free PSA (to calculate percent free PSA) is medically necessary per NCCN Guidelines (Version 2.2016) to help decide whether or not to perform a prostate biopsy for patients with an elevated PSA in the range of 3 – 10 or whether to perform a repeat prostate biopsy in men who are felt to be at high risk of prostate cancer despite a negative prostate biopsy. 

2)    4K Score or the PHI (Prostate Health Index) both include free PSA and offer no significant advantage over percent free PSA testing (per NCCN guidelines)—therefore these tests are not covered.

3)    PCA3 prostate cancer antigen—offers no significant advantage over percent free PSA testing (per NCCN guidelines)—therefore this test is not covered.

4)    ConfirmMDx—to decide on repeat prostate biopsy in men with a negative prostate biopsy offers no significant advantage over percent free PSA testing (per NCCN guidelines)—therefore this test is not covered.

B.   Carcinoembryonic antigen (CEA) is covered for members with a known history of  Colorectal and invasive breast cancers for any of the following:

1)    To detect asymptomatic recurrence after surgical and/or medical treatment (not as a screening test for any cancer); or

2)    As a preoperative prognostic indicator when it will assist in staging and surgical treatment planning; or

3)    To monitor response to treatment for metastatic cancer.

C.   Cancer antigen 125 (CA 125) levels for any of the following:

1)    As a screening test for ovarian cancer when there is a history of hereditary cancer syndrome (a pattern of clusters of ovarian cancer within two or more generations); or

2)    Diagnosis of ovarian cancer in women with new symptoms (bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, or urinary frequency and urgency) that have persisted for three or more weeks, where the clinician has performed a pelvic and rectal examination and suspects ovarian cancer; or

3)    As a preoperative diagnostic aid in women with ovarian masses that are suspected to be malignant, such that arrangements can be made for intraoperative availability of a gynecological oncologist if the CA 125 is increased; or 

4)    In members with known ovarian cancer, as an aid in the monitoring of disease, response to treatment, detection of recurrent disease, or assessing value of performing second-look surgery; or 

5)    In members with adenocarcinoma of unknown primary, to rule out ovarian cancer.

6)    In members with endometrial cancer who have extra-uterine disease.

D.   Serial measurements of CA 15-3 (also known as CA 27-29 or Truquant RIA) in following the course of treatment in women diagnosed with breast cancer, especially advanced metastatic breast cancer (an increasing CA 15-3 level may suggest treatment failure).

E.   CA 19-9 to monitor the clinical response to therapy or detect early recurrence of disease in members with known gastric cancer, pancreatic cancer, cholangiocarcinoma or adenocarcinoma of the ampulla of Vater.

F.    Serial measurements of human chorionic gonadotropin (HCG) to diagnose germ cell tumors in members with adenocarcinoma, or carcinoma not otherwise specified, involving mediastinal nodes, or to monitor treatment in members with known trophoblastic tumors (invasive Hydatidiform moles and choriocarcinomas) and germinal cell tumors (teratocarcinoma and embryonal cell carcinoma) of the ovaries or testes, or to monitor for relapse after remission is achieved.

G.   Serial measurements of alpha fetoprotein (AFP) to diagnose germ cell tumors in members with adenocarcinoma, or carcinoma not otherwise specified, involving mediastinal nodes; or the diagnosis and monitoring of hepatocellular carcinoma (e.g., before considering liver transplantation). 

H.   Serial measurements of AFP and HCG together to diagnose and monitor testicular cancer.

I.     Measurement of estrogen and progesterone receptors on primary breast cancers, and on metastatic lesions if the results would influence treatment planning. 

J.    Human epidermal growth factor receptor 2 (HER2) evaluation in breast cancer –

K.   The following markers are covered only when the result of the test(s) will directly determine the treatment course:

1)    K-ras (KRAS) mutation analysis to predict non-response to Cetuximab (Erbitux) and Panitumumab (Vectibix) in the treatment of metastatic colorectal cancer.

2)    Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) for the determination of prognosis in patients with newly diagnosed, node negative breast cancer.

3)    Steroid hormone receptor status in both pre-menopausal and post-menopausal members to identify individuals most likely to benefit from endocrine forms of adjuvant therapy and therapy for recurrent or metastatic breast cancer.

4)    CD117 (c-kit), for determining eligibility for treatment with imatinib mesylate (Gleevec).

5)    CD 20, for determining eligibility for anti-CD20 treatment (rituximab)

6)    CD 25, for determining eligibility for denileukin diftitox (Ontak) treatment.

7)    CD 33, for determining eligibility for anti-CD33 (gemtuzumab, Mylotarg) treatment.

8)    CD 52, for determining eligibility for anti-CD52 (Alemtuzumab, Campath) treatment.

L.    CD 31 immunostaining, for diagnosis of angiosarcoma.

M.  Cyclin D1, for diagnosis and predicting disease recurrence of mantle cell lymphoma.

N.   ZAP-70, for assessing prognosis and need for aggressive therapy in persons with chronic lymphocytic leukemia.

O.   Oncotype Dx (CPT 81519:also known as 21 gene mRNA RT-PCR test, in contrast to the non-covered CPT 81518: 11 gene mRNA RT-PCR test and the non-covered CPT 0045U or 81522: 12 gene mRNA RT-PCR) to assess necessity of adjuvant chemotherapy in women with recently diagnosed invasive breast tumors (once per lifetime), where all of the following criteria are met:

1)    Breast cancer is nonmetastatic (or 3 or fewer ipsilateral nodes involved per NCCN guidelines); and

2)    Breast tumor is estrogen receptor positive; and

3)    Breast tumor is HER2 receptor negative or breast tumor is HER2 receptor positive and less than 1 cm in diameter. (Rationale: adjuvant chemotherapy with Trastuzumab (Herceptin) is considered to be medically necessary regardless of an Oncotype Dx score for HER2 receptor positive lesions 1 cm or more in diameter); and

4)    Adjuvant chemotherapy is not precluded due to any other factor (e.g., advanced age and/or significant co-morbidities); and

5)    Member and physician (prior to testing) have discussed the potential results of the test and agree to use the results to guide therapy (i.e., member will forgo adjuvant chemotherapy if Oncotype Dx score is low).
Repeat Oncotype Dx testing or testing of multiple tumor sites in the same person has no proven value. Oncotype Dx is considered experimental and investigational for these and all other indications including its use in male breast cancer.  

P.   Myeloperoxidase (MPO) immunostaining, for diagnosis of acute myeloid leukemia.

Q.   Placental alkaline phosphatase (PLAP), to diagnose germ cell seminoma and non-seminoma germ cell tumors in unknown primary cancers.

2.  QualChoice considers the bladder tumor antigen (BTA) Stat test, the nuclear matrix protein (NMP22) test, the fibrin/fibrinogen degradation products (Aura-Tek FDP) test, or the UroVysion fluorescent in situ hybridization (FISH) test medically necessary in any of the following conditions:

A.   Follow-up of treatment for bladder cancer; or 

B.   Monitoring for eradication of bladder cancer; or 

C.   Recurrences after eradication.

QualChoice considers the BTA Stat test, the NMP22 test, the Aura-Tek FDP test, or the UroVysion fluorescent in situ hybridization (FISH) test experimental and investigational for screening of bladder cancer and all other indications.

3.  QualChoice considers the use of the ImmunoCyte immunohistochemistry test medically necessary as an adjunct to cystoscopy or cytology in the monitoring of persons with bladder cancer.

QualChoice considers the ImmunoCyte immunohistochemistry test experimental and investigational in the diagnosis of bladder cancer or for screening for bladder cancer in asymptomatic persons.

Codes Used In This BI:


PolypDx - urine ascorbate, carnitine & succinic acid


Overa GNRG – serum assay of 5 proteins (incl CA 125 II)


ExosomeDX prostate risk score


DEP Array TM HER2 for breast tumor tissue by FISH


Prostate (oncology) detection of 8 autoantibodies


Breast mRNA RT-PCR gene expression 12 genes


PCA3 Prostate Cancer Antigen


Unlisted Molecular Pathology Procedure




OncotypeDx for breast cancer, mRNA RT-PCR of 21 genes


4K Score


ConfirmMDx for Prostate Cancer


Unlisted multianalyte assay


Carcinoembryonic antigen


Assay of psa complexed


Assay of psa total


Assay of psa free


Assay of estrogen


Assay of progesterone


Immunoassay for tumor antigen (e.g., bladder tumor)


Immunoassay tumor ca 15-3


Immunoassay tumor ca 19-9


Immunoassay tumor ca 125


Immunoassay for tumor antigen, other antigen


Nuclear matrix protein 22

81522 – Onc(breast), mRNA, gene expression profiling by RT-PCR of 12 genes (8 content and 4 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as recurrence risk score


1.     QualChoice considers each of the following experimental and investigational. The peer reviewed medical literature does not support these tests as having sufficient sensitivity or specificity necessary to define their clinical role:

A.    CEA used for all other indications including any of the following:

                                    I.          As a screening test for any  cancer; or 

                                  II.          As a sole determinant to treat a colorectal or invasive breast cancer member with adjuvant therapy or systemic therapy for presumed metastatic disease; or

                                III.          For routine use of CEA alone for monitoring response to treatment of colorectal and invasive breast cancer when there are other simple tests available to indicate a response; or 

                                IV.          For diagnosis, prognosis, or monitoring of treatment in members with lung cancer; or

B.    CA 19-9 for all other indications including pancreatic pseudo cyst; colorectal, liver, breast, esophageal, or uterine cancer; or screening persons with primary sclerosing cholangitis without signs or symptoms of cholangiocarcinoma.

C.    AFP for the diagnosis of trophoblastic tumors and other oncologic indications. 

D.    CA 125 for all other indications including use as a screening test for colorectal cancer or ovarian cancer (other than as indicated above) or for differential diagnosis of members with symptoms of colonic disease. 

E.    Estrogen and progesterone receptors when used alone to assign a member with breast cancer to prognostic groupings since they are relatively weak predictors of long-term relapse and breast cancer related mortality rates. 

F.    Assaying for loss of heterozygosity (LOH) on the long arm of chromosome 18 (18q) or deleted in colon cancer (DCC) protein (18q-LOH/DCC) for colorectal cancer.

G.   Ova Check test

H.    Ova Sure

I.      Cell Search assay 

J.     Mamma print

K.    Path work Tissue of Origin test

L.     Ras oncogenes (except KRAS)

M.   Rotterdam Signature 76-gene Panel

N.    Breast Cancer Gene Expression Ratio (HOXB13:IL17BR)

O.   Gene Search™ Breast Lymph Node (BLN) assay

P.    Thymidylate synthase

Q.   Topographic genotyping (Pathfinder TG)

R.    Biomarker Translation (BT) test for breast cancer and other indications

S.    HE4 for ovarian cancer and other indications

T.    Vascular Endothelial Growth Factor (VEGF)

U.    Des-gamma-carboxy prothrombin (DCP) (also known as "prothrombin produced by vitamin K absence or antagonism II" [PIVKA II]) for diagnosing and monitoring hepatocellular carcinoma and other indications.

V.    Oncotype DX Colon Cancer Assay

W.  Any of the following circulating tumor markers also are considered experimental and investigational for screening asymptomatic subjects for cancer, diagnosis, staging, routine surveillance of cancer and monitoring the response to treatment:






Cathepsin-D, Cathepsin-L




Cyclin E (fragments or whole length)

Motility-related protein (MRP)




Multidrug resistance glycoprotein (Mdr1



Early prostate cancer antigen (EPCA)




Guanylyl cyclase C (GCC)

p53 (TP53)

Thrombospondin-1 (THBS-1)



PCA3 (DD3) / UpM3

Thymosin B15


Human kallikrein 2 (HK2)





Prostate stem cell antigen (PSCA)

Topoisomerase II Alpha (TOP2A)






M 26


Thymosin B15


M 29


Nuclear Matrix Protein 66 (NMP66)











Background Information Upon Request

1. Lein M, Stephan C, Jung K, et al. Relation of free PSA/total PSA in serum for differentiating between patients with prostatic cancer and benign hyperplasia of the prostate: Which cutoff should be used? Cancer Invest. 1998; 16(1):45-49. 2. Littrup PJ. Future benefits and cost-effectiveness of prostate carcinoma screening. American Cancer Society. Cancer. 1997; 80(9):1864-1870. 3. Gao X, Porter AT, Grignon DJ, et al. Diagnostic and prognostic markers for human prostate cancer. Prostate. 1997; 31(4):264-281. 4. Duffy MJ. PSA as a marker for prostate cancer: A critical review. Ann Clin Biochem. 1996; 33(Pt 6):511-519. 5. No authors listed. Ovarian cancer: Screening, treatment, and follow-up. NIH Consens Statement. 1994; 12(3):1-30. 6. Watine J, Charet JC. [Are the ATS (American Thoracic Society) and the ERS (European Respiratory Society) correct in not recommending routine tumor marker assays for screening, staging, or evaluation of non-small cell lung cancer?] Rev Mal Respir. 1999; 16(2):139-149. 7. Seifert JK Morris DI. Indicators of recurrence following cryotherapy for hepatic metastases from colorectal cancer. Br J Surg. 1999; 86(2):234-240. 8. Lagautriere F, Valvano L, Chaazl M, et al. Prognostic factors in colorectal adenocarcinoma. Ann Ital Chir. 1998; 69(4):491-497. 9. Hamm CM, Cripps C. Carcinoembryonic antigen in metastatic colorectal cancer. Clin Invest Med. 1998; 21(4-5):186-191. 10. Jessup JM, Loda M. Prognostic markers in rectal carcinoma. Semin Surg Oncol. 1998; 15(2):131-140. 11. Mazurek A. Niklinski J. Laudanski T. et al. Clinical tumor markers in ovarian cancer. Eur J Cancer Prev. 1998; 7(1):23-35. 12. American Society of Clinical Oncology. Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol. 1996; 14(10):2843-2877. 13. American Society of Clinical Oncology. 1997 update of recommendations for the use of tumor markers in breast and colorectal cancer. Adopted on November 7, 1997 by the American Society of Clinical Oncology. J Clin Oncol. 1998; 16(2):793-795. 14. Harrison LE, Guillem JG, Paty P, et al. Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: A multivariate analysis of 572 patients. J Am Coll Surg. 1997; 185(1):55-59. 15. Lamerz R, Stieber P, Fateh-Moghadam A. Serum marker combinations in human breast cancer. In Vivo. 1993; 7(6B):607-613. 16. American College of Physicians. Screening for ovarian cancer: Recommendations and rationale. Ann Intern Med. 1994 J; 121(2):141-142. 17. Carlson KJ. Screening for ovarian cancer. Ann Intern Med. 1994;121(2):124-132 18. Mogenson O. Prognostic value of CA 125 in advanced ovarian cancer. Gynecol Oncol. 1992; 44:207-212. 19. Patsner B, Mann WJ, Vissicchio M, Loesch M. Comparison of serum CA-125 and lipid-associated sialic acid (LASA-P) in monitoring patients with invasive ovarian adenocarcinoma. Gynecol Oncol. 1988; 30(1):98-103. 20. Makar AP, Kristensen GB, Bormer OP, Trope CG. CA 125 measured before a second-look laparotomy us an independent prognostic factor for survival in patients with epithelial ovarian cancer. Gynecol Oncol. 1992; 45(3):323-328. 21. Werner M, Faser C, Silverberg M. Clinical utility and validation of emerging biochemical markers for mammary adenocarcinoma. Clin Chem. 1993; 39(11 Pt 2):2386-2396. 22. Bates SE. Clinical Applications of serum tumor markers. Ann Intern Med. 1991; 115(8):623-638. 23. Steinberg W. The clinical utility of the CA19-9 tumor associated antigen. Am J Gastroenterol. 1990; 85:350-355. 24. Jorgensen LG, Osterlind K, Hansen HH, Cooper EH. Serum neuron specific enolase (NSE) is a determinant of response duration in small cell lung cancer. Br J Cancer. 1992; 66(3):594-598. 25. Johnson PW, Joel SP, Love S, et al. Tumor markers for prediction of survival and monitoring of remission in small cell lung cancer. Br J Cancer. 1993; 67(4):760-766. 26. Wobbes T, Thomas CM, Segers MF, Nagengast FM. Evaluation of seven tumor markers in the treatment sera of patients with gastric carcinoma. Cancer. 1992; 69(8):2036-2041. 27. Hayes DF. Serum tumor markers for breast cancer. Anticancer Drugs. 1995; 6(Suppl 2):26-27. 28. Coveney EC, Geraghty JG, Sherry F, et al. The clinical value of CEA and CA 15-3 in breast cancer management. Int J Biol Markers. 1995; 10(1):35-41. 29. Sharma S, Zippe CD, Pandrangi L, et al. Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA Stat. J Urol. 1999;162(1):53-57. 30. Pirtskalaishvili G, Konety BR, Getzenberg RH. Update on urine-based markers for bladder cancer. How sensitive and specific are the new noninvasive tests? Postgrad Med. 1999; 106(6):85-86, 91-94. 31. Sawczuk IS, Lee B. The mechanism and clinical applications of the NMP22 tumor marker immunoassay: A review. Am Clin Lab. 1999; 18(3):24-26. 32. Burchardt M, Burchardt T, Shabsigh A, et al. Current concepts in biomarker technology for bladder cancer. Clin Chem. 2000; 46(5):595-605. 33. Grocela JA, McDougal WS. Utility of nuclear matrix protein (NMP22) in the detection of recurrent bladder cancer. Urol Clin North Am. 2000; 27(1):47-51. 34. Brown FM. Urine cytology. Is it still the gold standard for screening? Urol Clin North Am. 2000; 27(1):25-37. 35. Bast RC Jr, Ravdin P, Hayes DF, et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: Clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001; 19(6):1865-1878. 36. Smith RA, Cokkinides V, von Eschenbach AC, et al. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin. 2002; 52(1):8-22. 37. Morabito A, Magnani E, Gion M, et al. Prognostic and predictive indicators in operable breast cancer. Clin Breast Cancer. 2003; 3(6):381-390. 38. Duffy MJ, van Dalen A, Haglund C, et al. Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer. 2003; 39(6):718-727. 39. Bubendorf L, Grilli B, Sauter G, et al. Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol. 2001; 116(1):79-86. 40. Sarosdy MF, Schellhammer P, Bokinsky G, et al. Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer. J Urol. 2002; 168(5):1950-1954. 41. Kruger S, Mess F, Bohle A, Feller AC. Numerical aberrations of chromosome 17 and the 9p21 locus are independent predictors of tumor recurrence in non-invasive transitional cell carcinoma of the urinary bladder. Int J Oncol. 2003; 23(1):41-48. 42. Society of Gynecologic Oncologists (SGO). Society of Gynecologic Oncologists statement regarding Ova Check™. Position Statements. Chicago, IL: SGO; February 7, 2004. Available at: Accessed June 4, 2004. 43. National Cancer Institute (NCI). Questions and answers: Ova Check ™ and NCI/FDA Ovarian Cancer Clinical Trials using proteomics technology. NCI News. Bethesda, MD: NCI; March22, 2004.Available at: 44. Permanente Medical Group. Ovacheck. Permanente Medical Group Physician Home Pages. San Francisco, CA: Kaiser Permanente; 2004. Available at: Accessed June 4, 2004. 45.  Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002; 359(9306):572-577. 46. U.S. Preventive Services Task Force (USPSTF). Screening for bladder cancer in adults. In: Guide to Clinical Preventive Services. Report of the U.S. Preventive Services Task Force. 3rd ed. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); June 2004. 47. American College of Obstetricians and Gynecologists (ACOG). The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer. ACOG Committee Opinion No. 280. Washington, DC: ACOG; December 2002. 48. National Cancer Institute (NCI). Ovarian Cancer (PDQ): Screening. Health Professional Version. Bethesda, MD: NCI; updated February 20, 2004. Available at: ovarian/health professional. Accessed September 22, 2004. 49. U.S. Preventive Services Task Force (USPSTF). Screening for ovarian cancer. In: Guide to Clinical Preventive Services. Report of the U.S. Preventive Services Task Force. 3rd ed. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); May 2004. 50. American College of Obstetricians and Gynecologists (ACOG). Position of the American College of Obstetricians and Gynecologists Committee on Gynecologic Practice Regarding Ova Check. Washington, DC: ACOG; February 25, 2004. 51. Andrews E. Ovacheck: Breakthrough or also ran? Nat Rev Med. 2004; 1(5). 52. Check E. Proteomics and cancer: Running before we can walk? Nature. 2004; 429(6991):496-497. 53. Diamandis EP. Ova Check: Doubts voiced soon after publication. Nature. 2004; 430(7000):611. 54. Gandini O, Luci L, Stigliano A, et al. Is DD3 a new prostate-specific gene? Anticancer Res. 2003; 23:305-308. 55. Schalken JA, Hessels D, Verhaegh G. New targets for therapy in prostate cancer: Differential display code 3 (DD3/PCA3), a highly prostate cancer specific gene. Urology. 2003; 62(suppl 5A):34-43. 56. Bussemakers MJG, van Bokhoven A, Verheagh GW, et al. DD3: A new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res. 1999; 59:5975-5979. 57. de Kok JB, Verhaegh GW, Roelofs RW et al. DDS (PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 2002; 62:2695-2698. 58. Hessels D, Klein Gunnewiek JM, van Oort I, et al. DD3 (PCA3) based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol. 2003; 44:8-16. 59. Abeloff MD, Armitage JO, Niederhuber JE, et al. Clinical Oncology. 3rd ed. Philadelphia, PA. Churchill Livingstone; 2004: 2369. 60. U.S. Food and Drug Administration (FDA), Center for Devices and Radiologic Health (CDRH). Cell Search™ Epithelial Cell Kit / Cell Spotter™ Analyzer. 510(k) no. K031588. Rockville, MD: FDA; January 21, 2004. 61. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004; 351(8):781-791. 62. Kahn HJ, Presta A, Yang LY, et al. Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: Correlation with disease stage. Breast Cancer Res Treat. 2004; 86(3):237-247. 63. Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004; 10(20):6897-6904. 64. Veridex, LLC. Cell Search™ [website]. Warren, NJ: Veridex; 2005. Available at: 65. Muller V, Pantel K. Bone marrow micro metastases and circulating tumor cells: Current aspects and future perspectives. Breast Cancer Res. 2004; 6(6):258-261. 66. Gilbey AM, Burnett D, Coleman RE, Holen I. The detection of circulating breast cancer cells in blood. J Clin Pathol. 2004; 57(9):903-911. 67. Ring A, Smith IE, Dowsett M. Circulating tumor cells in breast cancer. Lancet Oncol. 2004 Feb; 5(2):79-88. 68. Pantel K, Muller V, Auer M, et al. Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. Clin Cancer Res. 2003; 9(17):6326-6334. 69. Baker M, Gillanders WE, Mikhitarian K, et al. The molecular detection of micro metastatic breast cancer. Am J Surg. 2003; 186(4):351-358. 70. Weigelt B, Bosma AJ, Hart AA, et al. Marker genes for circulating tumor cells predict survival in metastasized breast cancer patients. Br J Cancer. 2003; 88(7):1091-1094. 71. Glas A S, Roos D, Deutekom M, et al. Tumor markers in the diagnosis of primary bladder cancer: A systematic review. J Urol. 2003; 169(6):1975-1982. 72. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004; 351(27):2817-2826. 73. Esteva FJ, Sahin AA, Coombes K, et al. Multi-gene RT-PCR assay for predicting recurrence in node negative breast cancer patients -- M.D. Anderson Clinical Validation Study [abstract]. Breast Cancer Res Treat. 2003; 82 (Suppl 1):S11. 74. Bast RC Jr, Hortobagyi GN. Individualized care for patients with cancer - a work in progress. N Engl J Med. 2004; 351(27):2865-2867. 75. Kamisawa T, Fukayama M, and Koike M, et al. Carcinoma of the ampulla of Vater: Expression of cancer-associated antigens inversely correlated with prognosis. Am J Gastroenterol. 1988; 83(10):1118-1123. 76. Matorras R, Rodriguez-Escuderoi FJ, Diez J, et al. Monitoring endometrial adenocarcinoma with a four tumor marker combination. CA 125, squamous cell carcinoma antigen, CA 19.9 and CA 15.3. Acta Obstet Gynecol Scand. 1992; 71(6):458-464. 77. Dorandeu A, Raoul JL, and Siriser F, et al. Carcinoma of the ampulla of Vater: prognostic factors after curative surgery: A series of 45 cases. Gut. 1997; 40:350-355. 78. Abrams RA, Grochow LB, Chakravarthy A, and et al. intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: Survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels. Int J Radiat Oncol Biol Phys. 1999; 44(5):1039-1046. 79. Kau SY, Shyr YM, Su CH, et al. Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers. J Am Coll Surg. 1999; 188(4):415-420. 80. Cherchi PL, Dessole S, Ruiu GA, et al. The value of serum CA 125 and association CA 125/CA 19-9 in endometrial carcinoma. Eur J Gynaecol Oncol. 1999; 20(4):315-317. 81. Rojas MP, Telaro E, Russo A, et al. Follow-up strategies for women treated for early breast cancer. Cochrane Database Syst Rev. 2000 ;( 4):CD001768. 82. Grossfeld GD, Litwin MS, and Wolf JS Jr, et al. Evaluation of asymptomatic microscopic hematuria in adults: The American Urological Association best practice policy--part II: Patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology. 2001; 57(4):604-610. 83. Segal R, Lukka H, Klotz LH, et al.; Cancer Care Ontario Practice Guidelines Initiative Genitourinary Cancer Disease Site Group. Surveillance programs for early stage non-seminomatous testicular cancer: A practice guideline. Can J Urol. 2001; 8(1):1184-1192. 84. Levine M, Moutquin JM, Walton R, Feightner J. Chemoprevention of breast cancer. A joint guideline from the Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiative`s Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. CMAJ. 2001; 164(12):1681-1690. 85. U.S. Preventive Services Task Force. Chemoprevention of breast cancer: Recommendations and rationale. Ann Intern Med. 2002; 137(1):56-58. 86. Jeffery GM, Hickey BE, Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2007 ;( 1):CD002200. 87. Garcia-Barcina M, Martin Bueno AE, de Bujanda Fernandez Pierola L, et al. Tumour markers in certain cancer locations. D-02-03. Vitoria-Gasteiz, Spain: Basque Office for Health Technology Assessment, Health Department Basque Government (OSTEBA); 2002. 88. Gupta S, Bent S, Kohlwes J. Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. Ann Intern Med. 2003;139(1):46-50. 89. Scottish Intercollegiate Guidelines Network (SIGN). Epithelial ovarian cancer. A national clinical guideline. SIGN Pub. No. 75. Edinburgh, Scotland: Scottish Intercollegiate Guidelines Network (SIGN); October 2003. 90. Baron TH, Mallery JS, Hirota WK, et al. The role of endoscopy in the evaluation and treatment of patients with pancreatic biliary malignancy. Gastrointestinal Endosc. 2003; 58(5):643-649. 91. Riley RD, Burchill SA, Abrams KR, et al. A systematic review and evaluation of the use of tumor markers in pediatric oncology: Ewing`s sarcoma and neuroblastoma. Health Technol Assess. 2003;7(5):1-162 92. Society for Surgery of the Alimentary Tract (SSAT). Operative treatment for chronic pancreatitis. Manchester, MA: SSAT; 2004. 93. Institute for Clinical Systems Improvement (ICSI). Breast cancer treatment. ICSI Healthcare Guidelines. Bloomington, MN: ICSI; September 2004. 94. Fradet Y, Saad F, Aprikian A, et al. uPM3, a new molecular urine test for the detection of prostate cancer. Urology. 2004; 64(2):311-315; discussion 315-316. 95. Tinzl M, Marberger M, Horvath S, Chypre C. DD3PCA3 RNA analysis in urine--a new perspective for detecting prostate cancer. Eur Urol. 2004; 46(2):182-186; discussion 187. 96. Pfister DG, Johnson DH, Azzoli CG, et al. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: Update 2003. J Clin Oncol. 2004; 22(2):330-353. 97. Otchy D, Hyman NH, Simmang C, et al. Practice parameters for colon cancer. Dis Colon Rectum. 2004; 47(8):1269-1284. 98. Saad F. UPM3: Review of a new molecular diagnostic urine test for prostate cancer. Can J Urol. 2005; 12 Suppl 1:40-43; discussion 99-100. 99. Bast RC Jr, Badgwell D, Lu Z, et al. New tumor markers: CA125 and beyond. Int J Gynecol Cancer. 2005; 15 Suppl 3:274-281. 100. Garner EI. Advances in the early detection of ovarian carcinoma. J Reprod Med. 2005; 50(6):447-453. 101. Fields MM, Chevlen E. Ovarian cancer screening: A look at the evidence. Clin J Oncol Nurs. 2006; 10(1):77-81. 102. Paik et al. Gene Expression and Benefit of Chemotherapy in Women with Node-Negative, Estrogen Receptor-Positive Breast Cancer J. Clin. Oncol. 2006 0 (2006), p. JCO.2005.04.7985v1 103. Habel LA, Shak S, Jacobs MK, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006; 8:R25 (doi: 10.1186/bcr1412). 104. Burstein HJ, Paik S, Ravdin PM, Albain KS. Adjuvant chemotherapy for patients with estrogen receptor-positive breast cancer. 2006 ASCO Educational Sessions. 2006:49-55. 105. Hultcrantz R, Olsson R, Danielsson A, et al. A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. J Hepatol. 1999; 30(4):669-673. 106. Chakravatri A, Zehr EM, Zietman AL, et al. Thymosin beta-15 predicts for distant failure in patients with clinically localized prostate cancer-results from a pilot study. Urology. 2000; 55(5):635-638. 107. Van de Vijver, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002; 347(25):1999-2009. 108. Nehls O, Gregor M, Klump B. Serum and bile markers for cholangiocarcinoma. Semin Liver Dis. 2004; 24(2):139-154. 109. Levy C, Lymp J, Angulo P, et al. The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis. Dig Dis Sci. 2005; 50(9):1734-1740. 110. Hutchinson LM, Chang EL, Becker CM, et al. Development of a sensitive and specific enzyme-linked immunosorbent assay for Thymosin beta15, a urinary biomarker of human prostate cancer. Clin Biochem. 2005; 38(6):558-571. 111. Locker GY, Hamilton S, Harris J, et al; ASCO. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006; 24(33):5313-5327. 112. Khatcheressian JL, Wolff AC, Smith TJ, et al; American Society of Clinical Oncology. American Society of Clinical Oncology 2006 updates of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006; 24(31):5091-5097. 113. National Horizon Scanning Centre (NHSC). NMP22 BladderChek proteomic assay for the detection of bladder cancer - horizon scanning technology note. Birmingham, UK: NHSC; 2006. 114. National Horizon Scanning Centre (NHSC). Prostate cancer gene 3 (Progensa PCA3) assay in the diagnosis of prostate cancer: Horizon Scanning Technology Briefing. Birmingham, UK: NHSC; 2006. 115. Parrella A, Mundy L, Merlin T, Hiller J. NMP22 BladderChek(TM) point-of-care diagnostic test for bladder cancer. Horizon Scanning Prioritizing Summary - Volume 9. Adelaide, SA: Adelaide Health Technology Assessment (AHTA) on behalf of National Horizon Scanning Unit (Health PACT and MSAC); 2005. 116. California Technology Assessment Forum (CTAF). Gene expression profiling as a guide for the management of early stage breast cancer. Technology Assessment. San Francisco, CA: CTAF; 2007. Available at: 117. Myers ER, Havrilesky LJ, Kulasingam SL, et al. Genomic tests for ovarian cancer detection and management. Evidence Report/Technology Assessment 145. Prepared by the Duke Evidence-Based Practice Center for the Agency for Healthcare Research and Quality (AHRQ). AHRQ Publication No. 07-E0001. Rockville, MD: AHRQ; October 2006. Available at: 118. Finkelstein SD, Marsh W, Demetris AJ, et al. Micro dissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma. Hepatology. 2003; 37(4):871-879. 119. Finkelstein SD, Przygodzki R, Pricolo VE, et al. Prediction of biologic aggressiveness in colorectal cancer by p53/K-ras-2 topographic genotyping. Mol Diagn. 1996; 1(1):5-28. 120. Kanbour-shakir A, Kounelis S, Papadaki H, et al. Relationship of p53 genotype to second-look recurrence and survival in ovarian epithelial malignancy. Mol Diagn. 1996; 1(2):121-129. 121. Ribeiro U, Safatle-Ribeiro AV, Posner MC, et al. Comparative p53 mutational analysis of multiple primary cancers of the upper aero digestive tract. Surgery. 1996; 120(1):45-53. 122. Przygodzki RM, Koss MN, Moran CA, et al. Pleomorphic (giant and spindle cell) carcinoma is genetically distinct from adenocarcinoma and squamous cell carcinoma by K-ras-2 and p53 analysis. Am J Clin Pathol. 1996; 106(4):487-492. 123. Safatle-Ribeiro AV, Ribeiro Junior U, Reynolds JC, et al. Morphologic, histologic, and molecular similarities between adenocarcinomas arising in the gastric stump and the intact stomach. Cancer. 1996; 78(11):2288-2299. 124. Przygodzki RM, Finkelstein SD, Keohavong P, et al. Sporadic and thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2. Lab Invest. 1997; 76(1):153-159. 125. Pricolo VE, Finkelstein SD, Bland KI. Topographic genotyping of colorectal carcinoma: From a molecular carcinogenesis model to clinical relevance. Ann Surg Oncol. 1997; 4(3):269-278. 126. Holst VA, Finkelstein S, Colby TV, et al. P53 and K-ras mutational genotyping in pulmonary carcinosarcoma, spindle cell carcinoma, and pulmonary blastoma: Implications for histogenesis. Am J Surg Pathol. 1997; 21(7):801-811. 127. Jones MW, Kounelis S, Papadaki H, et al. The origin and molecular characterization of adenoid basal carcinoma of the uterine cervix. Int J Gynecol Pathol. 1997; 16(4):301-306. 128. Jones MW, Kounelis S, Hsu C, et al. Prognostic value of p53 and K-ras-2 topographic genotyping in endometrial carcinoma: A clinic pathologic and molecular comparison. Int J Gynecol Pathol. 1997; 16(4):354-360. 129. Kounelis S, Jones MW, Papadaki H, et al. Carcinosarcoma (malignant mixed mullerian tumors) of the female genital tract: Comparative molecular analysis of epithelial and mesenchymal components. Hum Pathol. 1998; 29(1):82-87. 130. Ribeiro U Jr, Finkelstein SD, Safatle-Ribeiro AV, et al. p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma. Cancer. 1998; 83(1):7-18. 131. Finkelstein SD, Tiffee JC, Bakker A, et al. Malignant transformation in Sino nasal papillomas is closely associated with aberrant p53 expression. Mol Diagn. 1998; 3(1):37-41. 132. Holst VA, Finkelstein S, Yousem SA. Bronchioloalveolar adenocarcinoma of lung: Monoclonal origin for multifocal disease. Am J Surg Pathol. 1998; 22(11):1343-1350. 133. Pollack IF, Finkelstein SD, Burnham J, et al.; Children`s Cancer Group. Age and TP53 mutation frequency in childhood malignant gliomas: Results in a multi-institutional cohort. Cancer Res. 2001; 61(20):7404-7407. 134. Papadaki H, Kounelis S, Kapadia SB, et al. Relationship of p53 gene alterations with tumor progression and recurrence in olfactory neuroblastoma. Am J Surg Pathol. 1996; 20(6):715-721. 135. Przygodzki RM, Finkelstein SD, Langer JC, et al. Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome. Am J Pathol. 1996; 148(5):1531-1541. 136. Pricolo VE, Finkelstein SD, Wu TT, et al. Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon. Am J Surg. 1996; 171(1):41-46. 137. Finkelstein SD, Przygodzki R, Pricolo VE, et al. K-ras-2 topographic genotyping of pancreatic adenocarcinoma. Arch Surg. 1994; 129(4):367-73. 138. Lin X, Finkelstein SD, Zhu B, Silverman JF. Molecular analysis of multifocal papillary thyroid carcinoma. J Mol Endocrinol. 2008; 41(4):195-203. 139. Saad RS, Denning KL, Finkelstein SD, et al. Diagnostic and prognostic utility of molecular markers in synchronous bilateral breast carcinoma. Mod Pathol. 2008; 21(10):1200-1207. 140. Krishnamurti U, Sasatomi E, and Swalsky PA, et al. Analysis of loss of heterozygosity in atypical and negative bile duct brushing cytology specimens with malignant outcome: Are `negative` cytologic findings a representation of morphologically subtle molecular alterations? Arch Pathol Lab Med. 2007; 131(1):74-80. 141. Khalid A, Nodit L, Zahid M, et al. Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses. Am J Gastroenterol. 2006; 101(11):2493-2500. 142. Maheshwari V, Tsung A, Lin Y, et al. Analysis of loss of heterozygosity for tumor-suppressor genes can accurately classify and predict the clinical behavior of mucinous tumors arising from the appendix. Ann Surg Oncol. 2006; 13(12):1610-1616. 143. Lapkus O, Gologan O, Liu Y, et al. Determination of sequential mutation accumulation in pancreas and bile duct brushing cytology. Mod Pathol. 2006; 19(7):907-913. 144. Krishnamurti U, Sasatomi E, Swalsky PA, et al. Micro dissection-based mutational genotyping of serous borderline tumors of the ovary. Int J Gynecol Pathol. 2005; 24(1):56-61. 145. American Cancer Society (ACS). Ovarian cancer has early symptoms. First national consensus on common warning signs. ACS News Center. Atlanta, GA: ACS; June 14, 2007. Available at: 146. Berchuck A; Society for Gynecologic Oncologists. Ovarian cancer symptoms consensus statement. Chicago, IL: Society for Gynecologic Oncologists; 2007. Available at: Accessed July 6, 2007. 147. Goff BA, Mandel LS, Melancon CH, Muntz HG. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 2004; 291(22):2705-2712. 148. Daly MB, Ozols RF. Symptoms of ovarian cancer--where to set the bar? JAMA. 2004; 291(22):2755-2756. 149. Groskopf J, Aubin SM, Deras IL, et al. APTIMA PCA3 molecular urine test: Development of a method to aid in the diagnosis of prostate cancer. Clin Chem. 2006; 52(6):1089-1095. 150. Groskopf J, Nakanishi H, Deras IL, et al. The PCA3 score correlates with tumor volume but not prostate size, and can synergize with other patient information for predicting biopsy outcome. Abstrac 1709. Annual Meeting of the American Urological Association. Anaheim, CA; May 19-24, 2007. Available at: 151. van Gils MP, Hessels D, van Hooij O, et al The time-resolved fluorescence-based PCA3 test on urinary sediments after digital rectal examination; A Dutch multicenter validation of the diagnostic performance. Clin Cancer Res. 2007; 13(3):939-943. 152. Marks LS, Fradet Y, Deras IL, et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology. 2007; 69(3):532-535. 153. Gene-Probe, Inc. Gen-Probe PCA3 assay. Package Insert. San Diego, CA: Gen-Probe; April 2007. Available at: 154. Haese A, Van Poppel H, Marberger M, et al. The value of the PCA3 assay in guiding decision which men with a negative prostate biopsy need immediate repeat biopsy: Preliminary European data. Abstract. 22nd Annual EAU Congress. Berlin, Germany; March 21-24, 2007. European Association of Urology Web site. Available at: 155. National Horizon Scanning Center (NHSC). Prostate cancer gene 3 (Progensa PCA3) assay in the diagnosis of prostate cancer. Horizon Scanning Technology Briefing. Birmingham, UK: NHSC; December 2006. Available at: /PCA3%20for%20diagnosis%20of%20prostate%20cancer.pdf. Accessed August 21, 2007. 156. George B, Datar RH, Wu L, et al. p53 gene and protein status: The role of p53 alterations in predicting outcome in patients with bladder cancer. J Clin Oncol. 2007; 25(34):5352-5358. 157. Real FX. p53: It has it all, but will it make it to the clinic as a marker in bladder cancer? J Clin Oncol. 2007; 25(34):5341-5344. 158. Parekh DJ, Ankerst DP, Troyer D, et al. Biomarkers for prostate cancer detection. J Urol. 2007; 178(6):2252-2259. 159. Harris L, Fritsche H, Mennel R, et al; American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007; 25(33):5287-5312. 160. Svatek RS, Karam J, Karakiewicz PI, et al. Role of urinary Cathepsin B and L in the detection of bladder urothelial cell carcinoma. J Urol. 2008; 179(2):478-484; discussion 484. 161. Marchionni L, Wilson RF, Wolff AC, et al. Systematic review: Gene expression profiling assays in early-stage breast cancer. Ann Intern Med. 2008; 148(5):358-369. 162. Wolf I, Ben-Baruch N, Shapira-Frommer R, et al. Association between standard clinical and pathologic characteristics and the 21-gene recurrence score in breast cancer patients: A population-based study. Cancer. 2008; 112(4):731-736. 163. Australia and New Zealand Horizon Scanning Network (ANZHSN). Gene search™ breast lymph node (BLN) assay. Horizon Scanning Technology Prioritizing Summaries. Canberra, ACT: Australian Government, Department of Health and Ageing; May 2008. Available at: 164. Blumencranz P, Whitworth PW, Deck K, et al. Scientific Impact Recognition Award. Sentinel node staging for breast cancer: intraoperative molecular pathology overcomes conventional histologic sampling errors. Am J Surg. 2007; 194(4):426-432. 165. Blue Cross Blue Shield Association (BCBSA), Technology Evaluation Center (TEC). Use of gene search breast lymph node assay to detect sentinel node metastases in early stage breast cancer. TEC Assessment Program. Chicago, IL: BCBSA; 2007; 22(8). Available at: 166. U. S. Food and Drug Administration. Gene Search BLN Test kit. P060017. Rockville, MD: FDA. July 16, 2007. Available at: . 167. Viale G, Bosari S, Maxxarol G, et al. Intra-operative examination of axillary sentinel lymph nodes in breast carcinoma patients. Cancer 1999; 85(11):2433-2438. 168. Smeets A, Christiaens M. Implications of the sentinel lymph node procedure for local and systemic adjuvant treatment. Current Opinion in Oncology 2005; 17:539-544. 169. Viale G, Dell`Orto P, Biasi MO, et al. Comparative evaluation of an extensive histopathological examination and a real-time reverse-transcription-polymerase chain reaction assay for mamma globin and cytokeratin 19 on axillary sentinel lymph nodes of breast carcinoma patients. Ann Surg. 2008; 247(1):136-142. 170. Julian TB, Blumencranz P, Deck K, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer. J Clin Oncol. 2008; 26(20):3338-3345. 171. Visintin I, Feng Z, Longton G, et al. Diagnostic markers for early detection of ovarian cancer. Clin Cancer Res. 2008; 14(4):1065-1072. 172. Society of Gynecologic Oncologists (SGO)... Statement regarding Ova Sure. Chicago, IL: SGO; July 2, 2008. Available at: 173. Coradini D, Daidone MG. Biomolecular prognostic factors in breast cancer. Curr Opin Obstet Gynecol. 2004; 16(1):49-55. 174. Provista Life Sciences. The BT test and early breast cancer detection [website]. Phoenix, AZ: Provista Life Sciences; 2008. Available at: 175. Urban N, McIntosh MW, Andersen M, Karlan BY. Ovarian cancer screening. Hematol Oncol Clin North Am. 2003; 17(4):989-1005. 176. Lu KH, Patterson AP, Wang L, et al. Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res. 2004; 10(10):3291-3300. 177. Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005; 65(6):2162-2169. 178. Rosenthal AN, Menon U, Jacobs IJ. Screening for ovarian cancer. Clin Obstet Gynecol. 2006; 49(3):433-447. 179. Scholler N, Crawford M, Sato A, et al. Bead-based ELISA for validation of ovarian cancer early detection markers. Clin Cancer Res. 2006; 12(7 Pt 1):2117-2124. 180. Havrilesky LJ, Whitehead CM, Rubatt JM, et al. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol. 2008; 110(3):374-382. 181. Lowe KA, Shah C, Wallace E, et al. Effects of personal characteristics on serum CA125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2008; 17(9):2480-2487. 182. Otchy D, Hyman NH, Simmang C, et al. Practice parameters for colon cancer. Dis Colon Rectum. 2004; 47(8):1269-1284. 183. Compton CC. Pathology and prognostic determinants of colorectal cancer. Up-to-date [online serial]. Waltham, MA: Up-to-date; 2008. 184. BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Special Report: Pharmacogenomics of cancer-candidate genes. TEC Assessment Program. Chicago, IL: BCBSA; November 2007; 22(5). Available at: 185. Duffy MJ, van Dalen A, Haglund C, et al. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer. 2007 Jun; 43(9):1348-1360. 186. Shankaran V, Wisinski KB, Mulcahy MF, et al. The role of molecular markers in predicting response to therapy in patients with colorectal cancer. Mol Diagn Ther. 2008; 12(2):87-98. 187. Welch S, Kocha RB, Rumble K, et al., Gastrointestinal Cancer Disease Site Group. Cancer Care Ontario. The role of bevacizumab (Avastin) combined with chemotherapy in the treatment of patients with advanced colorectal cancer: Guideline recommendations. Evidence-based Series #2-25: Section 1. Toronto, ON: Cancer Care Ontario; May 2008. 188. National Institute for Health and Clinical Excellence (NICE). Bevacizumab and Cetuximab for the treatment of metastatic colorectal cancer. Technology Appraisal Guidance 118. London, UK: NICE; January 2007. Available at: 189. Secord AA, Darcy KM, Hutson A, et al; Gynecologic Oncology Group study. Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2007; 106(1):221-232. 190. Hellstrom I, Raycraft J, Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003; 63:3695. 191. Hellstrom I, Hellstrom KE. SMRP and HE4 as biomarkers for ovarian carcinoma when used alone and in combination with CA125 and/or each other. Adv Exp Med Biol. 2008;622:15-21 192. Moore RG, Brown AK, Miller MC, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008; 108(2):402-408. 193. Bast RC Jr, Brewer M, Zou C, et al. Prevention and early detection of ovarian cancer: Mission impossible? Recent Results Cancer Res. 2007; 174:91-100. 194. Scholler N, Crawford M, Sato A, et al. Bead-based ELISA for validation of ovarian cancer early detection markers. Clin Cancer Res. 2006; 12(7 Pt 1):2117-2124. 195. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007; 26:1324-1337. 196. Salgia R. Molecular markers in non-small cell lung cancer. Waltham, MA; Up-to-date [online serial]; 2008. 197. Reed JC. Bcl-2-family proteins and hematologic malignancies: history and future prospects. Blood. 2008; 111(7):3322-3330. 198. Bos JL. Ras oncogenes in human cancer: A review. Cancer Res. 1989; 49(17):4682-4689. 199. Lièvre A, Bachet JB, Le Corre D, et al. KRAS mutation status is predictive of response to Cetuximab therapy in colorectal cancer. Cancer Res. 2006; 66(8):3992-3995. 200. Di Fiore F, Blanchard F, Charbonnier F, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer. 2007; 96(8):1166-1169. 201. De Roock W, Piessevaux H, De Schutter J, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with Cetuximab. Ann Oncol. 2008; 19(3):508-515. 202. Lièvre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with Cetuximab. J Clin Oncol. 2008; 26(3):374-379. 203. Moroni M, Veronese S, Benvenuti S, et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol. 2005; 6(5):279-286. 204. Gonçalves A, Esteyries S, Taylor-Smedra B, et al. A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving Cetuximab-based treatment. BMC Cancer. 2008; 8(169). Available at: 205. Van Cutsem E, Lang I., D`haens G., et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without Cetuximab: The CRYSTAL experience. J Clin Oncol. 2008; 26: Abstr. 2. Available at: 206. Linardou H, Dahabreh IJ, Kanaloupiti D, et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: A systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008 Sep 17. [Epub ahead of print] 207. Bokemeyer C, Bondarenko I, Hartmann J, et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without Cetuximab: The OPUS experience. J Clin Oncol. 2008; 26: (May 20 Suppl; Abstr. 4000). Available at: 208. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for Panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26(10):1626-1634. 209. Blue Cross Blue Shield Association (BCBSA), Technology Evaluation Center (TEC). KRAS mutations and epidermal growth factor receptor inhibitor therapy in metastatic colorectal cancer. TEC Assessments in Press. Chicago, IL: BCBSA; September 2008. 210. BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Special report: Recent developments in prostate cancer genetics and genetic testing. TEC Assessments in Press. Chicago, IL: BCBSA; September 2008. 211. Nielsen KV, Ejlertsen B, Møller S, et al. The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D. Acta Oncol. 2008; 47(4):725-734. 212. Järvinen TA, Liu ET. Simultaneous amplification of HER-2 (ERBB2) and topoisomerase IIalpha (TOP2A) genes--molecular basis for combination chemotherapy in cancer. Curr Cancer Drug Targets. 2006; 6(7):579-602. 213. Pritchard KI, Messersmith H, Elavathil L, et al. HER-2 and topoisomerase II as predictors of response to chemotherapy. J Clin Oncol. 2008; 26(5):736-744. 214. Järvinen TA, Liu ET. Simultaneous amplification of HER-2 (ERBB2) and topoisomerase IIalpha (TOP2A) genes--molecular basis for combination chemotherapy in cancer. Curr Cancer Drug Targets. 2006; 6(7):579-602. 215. Perry J, Laperriere N, Zuraw L, et al; Neuro-oncology Disease Site Group. Adjuvant systemic chemotherapy, following surgery and external beam radiotherapy, for adults with newly diagnosed malignant glioma: A clinical practice guideline. Evidence-based series No.9-2. Toronto, ON: Cancer Care Ontario (CCO); November 2006. 216. Everhard S, Kaloshi G, Crinière E, et al. MGMT methylation: A marker of response to temozolomide in low-grade gliomas. Ann Neurol. 2006; 60(6):740-743. 217. Palanichamy K, Erkkinen M, Chakravarti A. Predictive and prognostic markers in human glioblastomas. Curr Treat Options Oncol. 2006; 7(6):490-504. 218. Idbaih A, Omuro A, Ducray F, et al. Molecular genetic markers as predictors of response to chemotherapy in gliomas. Curr Opin Oncol. 2007; 19(6):606-611. 219. Van den Bent MJ, Kros JM. Predictive and prognostic markers in neuro-oncology. J Neuropathol Exp Neurol. 2007; 66(12):1074-1081. 220. Stupp R, Hegi ME, Gilbert MR, et al. Chemo radiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol. 2007; 25(26):4127-4136. 221. Murat A, Migliavacca E, Gorlia T, et al. Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemo radiotherapy in glioblastoma. J Clin Oncol. 2008; 26(18):3015-3024. 222. Hegi ME, Liu L, Herman JG, et al. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol. 2008; 26(25):4189-4199. 223. Secord AA, Darcy KM, Hutson A, et al. Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: A Gynecologic Oncology Group study. Gynecol Oncol. 2007; 106(1):221-232. 224. Ghoneim C, Soula-Rothhut M, Rothhut B. Thrombospondin-1 in differentiated thyroid cancer: Dr. Jekyll and Mr. Hyde. Connect Tissue Res. 2008; 49(3):257-260. 225. Brostjan C, Gebhardt K, and Gruenberger B, et al. Neoadjuvant treatment of colorectal cancer with bevacizumab: the perioperative angiogenic balance is sensitive to systemic thrombospondin-1 levels. Clin Cancer Res. 2008; 14(7):2065-2074. 226. Garcia AA, Hirte H, Fleming G, et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: A trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol. 2008; 26(1):76-82. 227. List AF, Spier CM. Multidrug resistance in acute leukemia: A conserved physiologic function. Leuk Lymphoma. 1992; 8(1-2):9-14. 228. Yuen AR, Sikic BI. Multidrug resistance in lymphomas. J Clin Oncol. 1994; 12(11):2453-2459. 229. Solary E, Drenou B, Campos L, et al; Groupe Ouest EST Leucémies Aiguës Myéloblastiques. Quinine as a multidrug resistance inhibitor: A phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia. Blood. 2003; 15; 102(4):1202-1210. 230. Gruber A, Björkholm M, Brinch L, et al. A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia. Leuk Res. 2003; 27(4):323-328. 231. Takara K, Sakaeda T, Okumura K. An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy. Curr Pharm Des. 2006; 12(3):273-286. 232. Miyake M, Nakano K, Ieki Y, et al. Motility related protein 1 (MRP-1/CD9) expression: inverse correlation with metastases in breast cancer. Cancer Res. 1995; 55(18):4127-4131. 233. Erovic BM, Pammer J, Hollemann D, et al. Motility-related protein-1/CD9 expression in head and neck squamous cell carcinoma Head Neck. 2003; 25(10):848-857. 234. Mimori K, Kataoka A, Yoshinaga K, et al. Identification of molecular markers for metastasis-related genes in primary breast cancer cells. Clin Exp Metastasis. 2005; 22(1):59-67. 235. Mhawech P, Dulguerov P, Tschanz E, et al. Motility-related protein-1 (MRP-1/CD9) expression can predict disease-free survival in patients with squamous cell carcinoma of the head and neck. Br J Cancer. 2004; 90(2):471-475. 236. Mhawech P, Herrmann F, Coassin M, et al. Motility-related protein 1 (MRP-1/CD9) expression in urothelial bladder carcinoma and its relation to tumor recurrence and progression. Cancer. 2003; 98(8):1649-1657. 237. National Cancer Institute. Carcinoma of unknown primary treatment (PDQ®). Bethesda, MD: NCI; 2008. Available at: 238. U.S. Food and Drug Administration (FDA). FDA clears test that helps identify type of cancer in tumor sample. FDA News. Rockville, MD: FDA; July 31, 2008. Available at:  239. Dumur CI, Lyons-Weiler M, Sciulli C, et al. Interlaboratory performance of a microarray-based gene expression test to determine tissue of origin in poorly differentiated and undifferentiated cancers. J Mol Diagn. 2008; 10(1):67-77. 240. Pathwork Diagnostics [website]. Announcing the pathwork tissue of origin test [website]; Sunnyvale, CA. Available at: Accessed October 13, 2008. 241. Monzon FA, Dumur CI, Lyons-Weiler M, et al. Validation of a gene expression-based tissue of origin test applied to poorly differentiated and undifferentiated cancers. Abstract presented at the 13th Annual Meeting of the Association for Molecular Pathology, Los Angeles, CA, and November 7-10, 2007. 242. Flynn K. Bladder cancer surveillance. Brief Overview. Final Report. Boston, MA: Veterans Health Administration, Office of Patient Care Services, Technology Assessment Program; November 2007. 243. Nauseef WM, Olsson I, Arnljots K. Biosynthesis and processing of myeloperoxidase--a marker for myeloid cell differentiation. Eur J Haematol. 1988; 40(2):97-110. 244. Storr J, Dolan G, Coustan-Smith E, et al. Value of monoclonal anti-myeloperoxidase (MPO7) for diagnosing acute leukemia. J Clin Pathol. 1990; 43(10):847-849. 245. Dunphy CH, Polski JM, Evans HL, Gardner LJ. Evaluation of bone marrow specimens with acute myelogenous leukemia for CD34, CD15, CD117, and myeloperoxidase. Arch Pathol Lab Med. 2001; 125(8):1063-1069. 246. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002; 100(7):2292-2302. 247. Matsuo T, Kuriyama K, Miyazaki Y, et al. The percentage of myeloperoxidase-positive blast cells is a strong independent prognostic factor in acute myeloid leukemia, even in the patients with normal karyotype. Leukemia. 2003; 17:1538-1543. 248. British Committee for Standards in Hematology, Milligan DW, Grimwade D, Cullis JO, et al. Guidelines on the management of acute myeloid leukemia in adults. Br J Haematol. 2006; 135(4):450-474. 249. Storr J, Dolan G, Coustan-Smith E, et al. Value of monoclonal anti-myeloperoxidase (MPO7) for diagnosing acute leukemia. J Clin Pathol. 1990; 43(10):847-849. 250. British Committee for Standards in Hematology, Milligan DW, Grimwade D, Cullis JO, et al. Guidelines on the management of acute myeloid leukemia in adults. Br J Haematol. 2006; 135(4):450-474. 251. Liebman HA, Furie BC, Tong MJ, et al. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. NEJM. 1984; 310(22):1427-1431. 252. Fujiyama S, Izuno K, Gohshi K, et al. Clinical usefulness of des-gamma-carboxy prothrombin assay in early diagnosis of hepatocellular carcinoma. Dig Dis Sci. 1991; 36(12):1787-1792. 253. Weitz IC; Liebman HA. Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma: A critical review. Hepatology. 1993; 18(4):990-997. 254. Nomura F, Ishijima M, Horikoshi A, et al. Determination of serum des-gamma-carboxy prothrombin levels in patients with small-sized hepatocellular carcinoma: Comparison of the conventional enzyme immunoassay and two modified methods. Am J Gastroenterol. 1996; 91(7):1380-1383. 255. Aoyagi Y, Oguro M, Yanagi M, et al. Clinical significance of simultaneous determinations of alpha-fetoprotein and des-gamma-carboxy prothrombin in monitoring recurrence in patients with hepatocellular carcinoma. Cancer. 1996; 77(9):1781-1786. 256. Hamamura K, Shiratori Y, Shiina S, et al. Unique clinical characteristics of patients with hepatocellular carcinoma who present with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein. Cancer. 2000; 88(7):1557-1564. 257. Ikoma J, Kaito M, Ishihara T, et al. Early diagnosis of hepatocellular carcinoma using a sensitive assay for serum des-gamma-carboxy prothrombin: A prospective study. Hepatogastroenterology. 2002; 49(43):235-238. 258. Nagaoka S, Yatsuhashi H, Hamada H, et al. The des-gamma-carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma. Cancer. 2003; 98(12):2671-2677. 259. Yuan LW, Tang W, Kokudo N, et al. Measurement of des-gamma-carboxy prothrombin levels in cancer and non-cancer tissue in patients with hepatocellular carcinoma. Oncol Rep. 2004; 12(2):269-273. 260. Yuen MF, Lai CL. Serological markers of liver cancer. Best Pract Res Clin Gastroenterol. 2005; 19(1):91-99. 261. Nakamura S, Nouso K, Sakaguchi K, et al. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006; 101(9):2038-2043. 262. Toyoda H, Kumada T, Kiriyama S, et al. Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006; 4(1):111-117. 263. Shirabe K, Itoh S, Yoshizumi T, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol. 2007; 95(3):235-340. 264. Schwartz JM, Carithers RL. Clinical features and diagnosis of primary hepatocellular carcinoma. Up-to-date [online serial]. Waltham, MA: Up-to-date; 2008. 265. Sherman M. Surveillance for hepatocellular carcinoma in adults with chronic liver disease. Up-to-date [online serial]. Waltham, MA: Up-to-date; 2008. 266. National Comprehensive Cancer Network (NCCN). Hepatobiliary cancers. NCCN Clinical Practice Guidelines in Oncology v.2.2008. Fort Washington, PA: NCCN; October 2008. Available at: 267. Lüftner D, Possinger K. Nuclear matrix proteins as biomarkers for breast cancer. Expert Rev Mol Diagn. 2002; 2(1):23-31. 268. Wright T, McGechan A. Breast cancer: New technologies for risk assessment and diagnosis. Mol Diagn. 2003; 7(1):49-55. 269. Matritech, Inc. [website]. Newton, MA; Matritech; 2009. Available at: Accessed on January 27, 2009. 270. National Comprehensive Cancer Network (NCCN). Prostate Cancer Early Detection. NCCN Guidelines Version 2.2016. Fort Washington, PA: NCCN; accessed 3/2/2017. Available at:
Application to Products

This policy applies to all health plans and products administered by QualChoice, both those insured by QualChoice and those that are self-funded by the sponsoring employer, unless there is indication in this policy otherwise or a stated exclusion in your medical plan booklet.  Consult the individual plan sponsor Summary Plan Description (SPD) for self-insured plans or the specific Evidence of Coverage (EOC) or Certificate of Coverage (COC) for those plans or products insured by QualChoice.  In the event of a discrepancy between this policy and a self-insured customer’s SPD or the specific QualChoice EOC or COC, the SPD, EOC, or COC, as applicable, will prevail.  State and federal mandates will be followed as they apply.

Changes: QualChoice reserves the right to alter, amend, change or supplement benefit interpretations as needed.
This policy has recently been updated. Please use the index above or enter policy title in search bar for the latest version.