Tumor markers by Dr K Selvakumar

Tumor Markers

1. Dr. K. Selvakumar M.Sc., M.Phil., Ph.D., MBA(HM)., Medical Biochemist Tumor Markers

2. D e finition T umo r mar k e r s a r e su b st ances, usua l ly p r o t ei n s , t h a t a r e p r oduce d b y t h e bod y in r espon s e t o c ancer g r owt h o r b y the c ancer t i ss u e itse l f and th a t m a y b e d e t ec t ed i n b l ood , ur i ne , o r t i s s u e sa m p l e s. Som e tu m o r mar k e r s a r e spec i f i c f o r a part i cu l ar type o f c ance r , wh i l e o the r s a r e see n in s e v e r al c ancer ty p es.

3. Mo s t o f t h e w el l -kn o wn ma r k e r s m a y a l s o be el e v a t ed in no n- c ance r ou s c ond i t i ons. Conseq u e n t l y , tu m o r mar k e r s a l on e a r e not d iagno s t i c f o r c ance r . The r e a r e w el l -e st abl i sh e d tu m o r mar k e r s th a t a r e r out i n ely use d. Ma n y othe r po t e n t i al mar k e r s a r e s t i ll be i ng r esea r ched. Some markers cause great excitement when they are first discovered but, upon further investigation, prove to be no more useful than markers already in use.

4. Class i fi c a tion T umo r mar k e r s c an b e clas s i f ied in t w o g r ou p s : Cancer - spec i f i c mar k e r s T i ss u e- spec i f i c mar k e r s

5. Cancer -specif i c ma r k e r s R el a t ed t o the p r esence o f cer t ain c ance r ous t i s s ue the s e mar k e r s mig h t no t b e spec i f i c in mak i n g a d iagnosis us e fu l in the f o ll o w - u p o f t r e a t ed p a t i e n ts t o describ e p r og r ess o f the d i sease r espon s e t o t r e a tme n t E x amp l es o f the s e m ar k e r s a r e C E A , C A 1 9 - 9 , C A 125

6. CEA is used as a tumor marker. An elevated or rising CEA level indicates cancer progression or recurrence. The CEA, test measures the amount of this protein that may appear in the blood of some people who have certain kinds of cancers, especially cancer of the large intestine (colon and rectal cancer). It may also be present in people with cancer of the pancreas, breast, ovary, or lung. . Carcinoembryonic antigen (CEA)

7. Tis s u e -specific ma r k e r s R el a t ed t o spec i f i c ti s s ue s wh i ch h a v e d e v el ope d c ancer the s e s ub st ances a r e no t spec i f i c ally r el a t ed t o the tu m o r , and m a y b e p r ese n t a t el e v a t ed l e v els when n o c ancer is p r ese n t. But un li k e the p r e vi ou s g r oup , el e v a t ed l e v els po i n t t o a s p eci f i c ti s s u e be i n g a t f aul t E x amp l es i nc l ud e P S A , b e t a - H C G ,AF P - L3 , and T h y r og l obu li n

8. Alpha Feto Protein (AFP) AFP is a major plasma protein (glycoprotein) produced by the yolk sac and the liver during fetal development that is thought to be the fetal form of serum albumin . AFP is measured in pregnant women through the analysis of maternal blood or amniotic fluid, as a screening test for a subset of developmental abnormalities -Increased in open neural tube defects and omphalocoele -Decreased in Down syndrome

9. It used as a biomarker to detect a subset of tumors in non-pregnant women, men , and children. A level above 500 ng/ml of AFP in adults can be indicative of : Hepatocellular carcinoma Germ cell tumors Metastatic cancers of the liver

10. Gen e Mu t a tions Som e peop le a r e a t a h igher ri s k f o r part i cu l ar c ance r s be c ause th e y h a v e i nher i t ed a g en e t i c mu t a t i on Wh i le no t c ons i d e r ed t umo r ma k e r s , the r e a r e t e s ts t h a t l oo k f o r these m u t a t i on s in o r de r t o e s t i m a t e t h e ri s k o f de v el op i n g a par t icu l ar type o f c ance r B R C A 1 and B R C A 2 a r e e x amp l es o f g ene mu t a t i ons r el a t ed t o an i nher i t ed ri s k o f b r ea s t c ancer and o v arian c ance r

11. US E S T umo r mar k e r s a r e no t d iagno s t i c in th e m s el v es D e f i n i t i v e d iagnos i s o f c anc e r is made b y l ook i n g a t ti s su e b i o p s y spec i mens unde r a m i c r os c op e. H o w e v e r , tu m o r mar k e r s p r ov i d e i n f orm a t i on th a t c an b e use d t o: Screen : PSA testing may be used to screen for prostate cancer Diagnose : CA-125 for ovarian cancer Stage Determine Prognosis Guide Treatment : Breast cancer patients who are Her2/ neu positive are more likely to respond to Herceptin treatment Monitor Treatment AFP in a child previously treated for teratoma suggests relapse with endodermal sinus tumor. Determine Recurrence

12. P r o s t a t e Specific A n ti g e n (P S A) the on ly tumor mar k er t o g ain wi de acce p t ance as a sc r een i n g t e s t is P S A f o r p r o s t a t e c ancer in men. E v en wi t h P S A th e r e i s c o n t i nue d deb a t e among e xpert s and n a t i ona l o r g ani z a t i ons o v er the us e fu l nes s o f t h is t e s t f o r sc r een ing a s ym p t om a t i c me n . SCREENING T E S T S

13. Other markers are either not specific enough (too many false positive, leading to expensive and unnecessary follow-up testing) or they are not elevated early enough in the disease process to be useful for screening Other Markers

14. Common Tumor Markers Currently in Use

15. AFP (A l ph a - f e t o p r o t ei n) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE L i v e r , g erm cel l c ancer of o v ar i es o r t e s t es Al s o el e v at ed du r i n g p r egnancy He l p di agnose, mon i t or t r e a tme n t, and d et erm i n e r ecur r ence Bl ood

16. CA 15-3 (Cancer antigen 15-3) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Breast cancer and lung , ovarian Also elevated in benign breast conditions Stage disease, monitor treatment, and determine recurrence Blood

17. B2M (Beta-2 microglobulin) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Multiple myeloma and lymphomas Crohn's disease and hepatitis Determine prognosis Bl ood

18. CA 19-9 (Cancer antigen 19-9) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Pancreatic, sometimes colorectal and bileducts Pancreatitis and inflammatory bowel disease Stage disease, monitor treatment, and determine recurrence Blood

19. CA-125 (Cancer antigen 125) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Ovarian endometriosis , some other benign diseases Help diagnose, monitor treatment, and determine recurrence Blood

20. Calcitonin CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Thyroid medullary carcinoma pernicious anemia and thyroiditis Help diagnose, monitor treatment, and determine recurrence Blood

21. CEA ( Carcinoembryonic antigen) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Colorectal, lung, breast, thyroid, pancreatic, liver, cervix , and bladder hepatitis, COPD, colitis, pancreatitis, and in cigarette smokers Monitor treatment and determine recurrence Blood

22. Chromogranin A ( CgA ) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Neuroendocrine tumors (carcinoid tumors, neuroblastoma) May be most sensitive tumor marker for carcinoid tumors To help diagnose and monitor Blood

23. hCG (Human chorionic gonadotropin) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Testicular and trophoblastic disease Elevated in pregnancy, testicular failure Help diagnose, monitor treatment, and determine recurrence Blood, urine

24. Her-2/ neu CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Testicular and trophoblastic disease Elevated in pregnancy, testicular failure Help diagnose, monitor treatment, and determine recurrence Blood, urine

25. Monoclonal immunoglobulins CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Multiple myeloma and WaldeŶstroŵ’s macroglobulinemia Overproduction of an immunoglobulin or antibody, usually detected by protein electrophoresis Help diagnose , monitor treatment, and determine recurrence Blood , urine

26. PSA (Prostate specific antigen), total and free CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Prostate benign prostatic hyperplasia, prostatitis and with age Screen for and help diagnose, monitor treatment, and determine recurrence Blood

27. Thyroglobulin CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Thyroid Used after thyroid is removed to evaluate treatment Determine Blood

28. OTHER TUMOR MARKERS LESS WIDELY USED

29. BTA (Bladder tumor antigen) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Bladder Not widely available, but gaining acceptance Help diagnose and determine recurrence Urine

30. Prostatic acid phosphatase (PAP) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Ovarian No evidence that it is better than CA-125 but may be useful when combined with it; still being studied Help diagnose Blood

31. CA 72-4 (Cancer antigen 72-4) CA N CE R S WH A T E L SE? WHE N /H O W USED US U AL S AMPLE Metastatic prostate cancer, myeloma, lung cancer Not widely used anymore; elevated in prostatitis and other conditions Help diagnose Blood