Tumor markers in gynaecology

tumour markers in gynaecology

1. Tumor Markers BY: DR. MONICAPREET KAUR MODERATOR : DR. SHALINI K. MAKKAR

2. Tumor markers are soluble glycoproteins that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. The various tumor markers differ in their usefulness for screening, diagnosis, prognosis, assessing therapeutic response, and detecting recurrence.

3. Characteristics of an ideal tumor marker It should be produced only by the tumor cells High sensitivity and specificity for cancerous growth Correlation of marker level with tumor size . Its measurement either in blood or urine should be sensitive enough to detect microscopic or subclinical disease. Inexpensive and acceptable

4. TYPES OF GYNECOLOGIC TUMOR MARKERS Enzymes or isoenzymes ( ALP , LDH ) Hormones ( inhibin , AMH , hCG , GAT ) Oncofetal proteins (AFP , CEA ) Carbohydrate epitopes ( CA 125 , CA 15-3 , CA19-9 ) Receptors (estrogen , progestrone and testosterone ) Serum and tissue proteins ( TAG 72 , HE 4 Others ( SCC A , OV X1 , OV X2 , CELL FREE DNA , CYFRA 21-1 )

5. CA 125 High molecular weight glycoprotein. Developed through immunization of mice with cells from ovarian carcinoma line to produce OC 125 monoclonal antibody . Half life of 20 days value higher than 35 U/mL is suggestive of epithelial ovarian cancer . CA 125 is elevated in 90 % of malignant non mucinous tumors . It is used for screening , monitoring of patient during chemotherapy and for follow up of epithelial cancers of ovary.

6. Benign condition with raised CA 125: Fibroid Adenomyosis Endometriosis Genital TB PID Cirrhosis Hepatitis Early pregnancy ( 25 %) Pleural effusion Pericarditis Maligniant conditions with raised CA 125 : Epithelial ovarian carcinoma Ca endometerium Adenocarcinoma of cervix , and fallopian tube(85 %) Uterine sarcomas Immature teratoma cancers of breast, lung , colon

7. Human Epididymis 4 protein Newer maker of ovarian cancers Minimally produced by normal ovarian tissue Elevated in epithelial ovarian cancer . More sensitive and specific than CA 125 . Normal range < 150 pM .

8. ROMA Risk of o varian malignancy algorithm Classifies patient with low or high risk of malignancies Uses CA 125 , HE 4 and menopausal status Interpretation is made by algorithm on website , calculator or by using mobile application .

9. Other BIOMARKER panels OVA 1 : Increased CA125, beta 2 microglobulin decreased transferrin, transthyretin and apolipoprotein A Overa : combines CA 125 , HE 4 , transferrin , apolipoprotein A and FSH RMI( risk of malignancy index ) includes CA125 , pelvic USG and menopausal status.

10. ALPHAFETOPROTEIN normal fetal serum Glycoprotein synthesized by the liver, yolk sac, and gastrointestinal tract. Performs some of function of albumin in fetal circulation. Started decreasing after birth , achieved adult level after 6 months to 1 year of age Half life : 5 days AFP concentration in adult serum is less than 20 ng / mL . Physiological conditions with elevated AFP : PREGNANCY AGE <1 YEAR

11. AFP raised in Germ cell tumor like Yolk sac tumor Immature teratoma Embryonal ca polyembryoma Hepatocellular carcinoma Hepatoblastoma Other conditions : Hepatitis Cirrhosis Biliary tract obstruction Alcoholic liver disease Colitis Ataxia telengectasia

12. HUMAN CHORIONIC GONADOTROPHINS Multiple forms in serum ( heterodimer , free alpha , free beta , various degradation products ) Level <5 u/l Half life 16 – 24 hours

13. Physiological elevated in : Pregnancy Benign condition with raised HCG : Pituitary adenoma Malignant conditions with raised HCG : Gestational trophoblastic disease germ cell tumor ( dysgerminoma ( 5 %) , embryonal carcinoma, mixed germ cell tumor , polyembroma ) Non gestational ovarian choriocarcinoma

14. CHRIOEMBRYONIC ANTIGEN Highly glycosylated cell surface protein involved in intracellular adhesions Normally produced by gastrointestinal tissue during fetal life but stops before birth . Most commonly associated with colorectal cancers

15. Benign conditions with elevated CEA : Smokers Hepatitis Cirrhosis Pulmonary emphysema Bronchitis Ulcerative colitis Renal disease Malignant conditions with raised CEA : Ovarian ( serous , endometeroid ) Cervical ( squamous cell type ) ADENOCARCINOMA of colon , rectum breast , lung

16. CA 19 9 Normal serum concentration < 37u/ml Half life 24 hours Non specific , helps in early detection of recurrance Malignacies associated with high CA19 9 ENDOMETERIAL CANCER (35%) Immature teratoma Pancreatic adenocarcinoma Gastric adenocarcinoma Colorectal cancers Bile duct cancers Hepatoma Benign conditions with raised CA 19 9: Chronic pancreatitis Cirrhosis Acute cholangitis Bile duct stenosis Cystic fibrosis Diabetes mellitus

17. TESTOSTERONE AND DHEAS Elevated levels of both are strongly suggestive of SCSTS with signs and symptoms of virilization . Serum testosterone level > 150g/dl and Serum DHEAS levels > 8000g/l strongly suggestive of androgen secreting tumor.

18. INHIBIN Peptide hormone normally produced by ovarian granulosa cells . Level reaches peak level follicular phase of menstural cycle and undetectable in menopausal women Elevated in granulosa cell tumors and mucinous epithelial ovarian carcinoma . Both inhibin A and B are raised but inhibin B levels are usually elevated in higher propotion . Normal levels INHIBIN A < 5ng/l INHIBIN B < 15 ng /l

19. ANTI MULLERIAN HORMONE Peptide produced by granulosa cells of primordial follicle and by sertoli cells of testis . Caused mullerian duct regression during male sex defferentiation . Helps in oocyte maturation and follicular development and recruitment of dominant follicle. Elevated in Granulosa cell tumor ( 75%)

20. SCCA Elevated in CARCINOMA CERVIX , VULVAR AND VAGINAL SQUAMOUS CELL CARCINOMA Elevated levels correlate with tumor size, stage , stromal invasion , and lymph node status in carcinoma cervix . Not specific Monitor tumor response and predict tumor reoccurrence.

21. MARKER TISSUE OF ORIGIN HCG TROPHOBLASTIC and GERM CELL TUMOR ( DYSGERMINOMA AND EMBRYONAL CARCINOMA AFP GERM CELL ( YOLK SAC AND IMMATURE TERATOMA TUMOR CA 125 OVARIAN EPITHELIAL TUMOR , ENDOMERTERIAL ADENOCARCINOMA , CA CERVIX HE 4 SEROUS EPITHELIAL OVARIAN TUMOR CEA OVARIAN ( SEROUS , ENDOMETEROID),CERVICAL (SQUAMOUS CELL ) TUMOR ASSOCIATED GLYCOPROTEIN 72 OVARIAN EPITHELIAL TUMOR MACROPHAGE COLONY STIMULATING FACTOR OVARIAN EPITHELIAL TUMOR SQUAMOUS CELL CARCINOMA ANTIGEN CA CERVIX , VULVAR AND VAGINAL SQUAMOUS CELL CARCINOMA LDH OVARIAN GERM CELL TUMORS CA 15-3 OVX 1, OVX 2, HE 4 , Her 2/ neu OVARIAN EPITHELIAL TUMOR

22. MARKERS TISSUE OF ORIGIN GLACTOSYL TRANSFERASE ASSOCIATED WITH TUMOR TO DIFFERENTIATE OVARIAN CANCER FROM ENDOMETEROSIS ESTROGEN , PROGESTRONE , TESTOSTERONE SEX CORD STROMAL TUMOR ( SCSTS) INHIBIN, ANTIMULLARIAN HORMONE GRANULOSA CELL TUMOR ( SCSTS) CELL FREE DNA OVARIAN CARCINOMA HE 2 ENDOMETERIAL CANCER CYFRA 21-1 ENDOMETERIAL CANCER , OVARIAN CANCER

23. THANK YOU