Tumor markers

1. Tumor markers Eleni Galani Medical Oncologist

3. Tumor markers • Tumor markers are usually proteins which are produced from cancer cells or as response to cancer • Cancer specific • Tissue specific

4. Tumor markers • Cancer specific of certain cancerous tissue BUT large overlap (low specificity) • Tissue specific i.e PSA, AFP, B-HCG, thyroglobulin

5. In oncology tumor markers are used: • Screening i.e PSA • Monitoring i.e AFP • Diagnosis (when biopsy is not feasible) • Determine prognosis

6. Tumor markers: CEA • Complex glycoprotein that is associated with the plasma membrane of tumor cells, from which may be released in the blood • Elevated specially in Colon cancer, But Also in Pancreatic, Gastric, Lung, breast and Ovarian cancer • ALSO in cirrhosis, inflammatory bowel disease, chronic lung disease, pancreatits, 19% of smokers, 3% of healthy population

7. Tumor markers: CEA • NOT satisfactory for screening for a healthy population • Monitor of recurrence • Monitor of treatment

8. Tumor markers: Ca-125 • 80% of nonmucinus ovarian cancer detected by monoclonal antibody • Elevated in Ovarian, Endometrial, Pancreatic, Lung, Breast, Colon, Menstruation, Pregnancy, Endometriosis and other gynecological and non conditions.

9. Tumor markers: Ca-125 • Useful in monitoring ovarian cancer recurrence & treatment • Not useful foe screening • Screening of high risk population (BRCA1-2 Carriers)

10. Tumor markers: CA 19-9 • 21-42% elevated in gastric ca • 20-40% elevated in colonic ca • 71-93% elevated in pancreatic • Useful for differentiated benign from malignant disease

11. Tumor markers: PSA • Prostate Specific Antigen: Glycoprotein • Ideal for tumor marker, high tissue specificity • High sensitivity for prostate cancer, also elevated in benign prostate hypertrophy & prostatitis • Useful in diagnosis

12. Tumor markers: PSA Useful for: • Diagnosis of prostate cancer • Prognostic factor • Monitor recurrence & response to treatment • ?Screening of prostate cancer (+rectal examination)

13. Screening for Prostate Cancer: Recommendations and Rationale U.S. PREVENTIVE SERVICES TASK FORCE The USPSTF found good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes. The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for prostate cancer PSA testing or digital rectal examination (DRE).

14. Tumor markers: AFP • Normal serum fetal protein synthesized by the liver, yolk sac, gastrointestinal tract • Heptocellular cancer: diagnosis (>500) screening of high risk population

15. Tumor markers: AFP • Testicular germ cell tumor (embrional or endodermal): diagnosis monitor of recurrence & response prognostic marker (>100.000 –high risk) • Less frequent elevated: pancreatic ca Gastric ca Colonic ca Bronchogenic ca

16. 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 American Society of Clinical Oncology Tumor Markers Expert Panel

17. CEA as a Marker for Breast Cancer 1997 Recommendation: CEA is not recommended for screening, diagnosis, staging, or routine surveillance of breast cancer patients after primary therapy. 2000 Update: None. 2000 Recommendation: No change. 1997 Recommendation: Routine use of CEA for monitoring response of metastatic disease to treatment is not recommended. However, in the absence of readily measurable disease, a rising CEA may be used to suggest treatment failure. 2000 Update: Routine use of CEA for monitoring response of metastatic disease to treatment is not recommended. However, in the absence of readily measurable disease, or an elevated MUC-1 marker (CA 15-3 and/or CA 27.29), a rising CEA may be used to suggest treatment failure. 2000 Recommendation: No change.

18. CA 15-3 as a Marker for Breast Cancer 1997 Recommendation : Present data are insufficient to recommend CA 15–3 for screening, diagnosis, staging, or surveillance after primary treatment. Although a rising CA 15–3 level can detect recurrence after primary treatment, the clinical benefit is not established; therefore, it cannot be recommended. 2000 Recommendation: No change. CEA as a Marker for Breast Cancer

19. c - erb B -2 (HER-2/neu) as a Marker for Breast Cancer 1997 Recommendation: Present data are insufficient to recommend the use of c-erbB-2 (HER-2/neu) gene amplification or overexpression for management of patients with breast cancer. 2000 Recommendation: c-erbB-2 overexpression should be evaluated on every primary breast cancer either at the time of diagnosis or at the time of recurrence. Measures of c-erbB-2 amplification may also be of value.

20. CEA as a Marker for Colorectal Cancer 1997 Recommendation : CEA is not recommended to be used as a screening test for colorectal cancer. 2000 Recommendation : No change. 1997 Recommendation : CEA may be ordered preoperatively in patients with colorectal carcinoma if it would assist in staging and surgical treatment planning. Although elevated preoperative CEA (> 5 ng/mL) may correlate with poorer prognosis, data are insufficient to support the use of CEA to determine whether to treat a patient with adjuvant therapy. 2000 Recommendation : No change.

21. CEA as a Marker for Colorectal Cancer 1997 Recommendation : If resection of liver metastases would be clinically indicated, it is recommended that postoperative serum CEA testing may be performedevery 2 to 3 months in patients with stage II or III disease for 2 or more years after diagnosis. An elevated CEA, if confirmed by retesting, warrants further evaluation for metastatic disease but does not justify the institution of adjuvant therapy or systemic therapy for presumed metastatic disease. 2000 Recommendation : No change.

22. CEA as a Marker for Colorectal Cancer 1997 Recommendation : Present data are insufficient to recommend routine use of the serum CEA alone for monitoring response to treatment. If no other simple test is available to indicate a response,CEA should be measured at the start of treatment for metastatic diseaseand every 2 to 3 months during active treatment. Two values above baseline are adequate to document progressive disease even in the absence of corroborating radiographs. CEA is regarded as the marker of choice for monitoring colorectal cancer. 2000 Recommendation : No change.

23. CA 19-9 As a Marker for Pancreatic Cancer 2006 recommendation for use of CA 19-9 as a screening test. CA 19-9 is not recommended for use as a screening test for pancreatic cancer. 2006 recommendation for use of CA 19-9 to determine operability. The use of CA 19-9 testing aloneis not recommended for use in determining operability or the results of operability in pancreatic cancer. 2006 recommendation for use of CA 19-9 to provide evidence of recurrence. CA 19-9 determinations by themselves cannot provide definitive evidence of disease recurrence without seeking confirmation with imaging studies for clinical findings and/or biopsy.

24. CA 19-9 As a Marker for Pancreatic Cancer 2006 recommendation for use of CA 19-9 for monitoring response to therapy. Present data are insufficient to recommend the routine use of serum CA 19-9 rules alone for monitoring response to treatment. However, CA 19-9 can be measured at the start of treatment for locally advanced metastatic disease and every 1 to 3 monthsduring active treatment. If there is an elevation in serial CA 19-9 determinations, this may be an indication of progressive disease, and confirmation with other studies should be sought.