TUMOR MARKERS WHAT ARE THEY WHY ARE THEY HOW TO USE THEM

1. Serum tumor markers
tool for the management of cancer
DR.PANKAJ GUPTA

2. OBJECTIVES
• What are they?
• Why are they used?
• How are they used?

3. A BREIF HISTORY OF TUMOR MARKERS
• In 1875, H. Bence Jones described and named Multiple Myeloma
and Bence Jones Proteinuria
• In 1960, immunoassay techniques were developed
• In 1975, monoclonal antibodies were developed by hybridoma
technique

4. TUMOUR MARKERS: A DEFINITION
“Tumour markers are molecules that can be detected in blood,
body fluids or tissue of the host and which are produced either as
a response to cancer or by cancer cells themselves.”

5. WHAT MAKES AN IDEAL TUMOR MARKER ?
• 100% sensitive and specific
• Having a short half life
• Easily measurable and easily reproducible
• Proportionate to the size of the tumour
• Cost-effective

6. CLASSIFICATION
Tumour
markers
Tumour
associated
proteins
Oncofetal
antigens
Epithelial
antigens
Oncoproteins/
Oncogenes
Enzymes
Hormones
Tumour
suppressor
genes
Adhesion
molecules

7. CLINICAL IMPLICATION
Screening
Diagnosis
Staging
Prognosis
Monitoring
treatment
Recurrence

8. RECONMENDATIONS FOR ORDERING
TUMORS MARKES
• Do serial testing
• Same lab
• While monitoring recurrence, make sure the tumour marker level was
elevated before surgery

9. • Considering half life while interpreting the result
• Know the metabolism of the tumour marker
• Panel testing is better than testing a single marker

10. α- FETO PROTEIN (AFP)
• Glycoprotein
• Secreted from fetal yolk sac, liver and gastrointestinal tract
• Normal levels are <15 ng/ml (HL= 3-5 days)
• Resembles, structurally as well as genetically to albumin

11. INTERPRETATION
1. Hepatocellular carcinoma
• Screening tool in high prevalence areas
• Levels > 500 ng/ml in adults
• Markedly increased levels (>1000 ng/ml) s/o tumors size > 3cm
• High initial concentrations correlate with poor prognosis

12. • Failure to return normal after surgery indicates incomplete resection
or presence of mets
• Post operative decrease in concentration followed by increase
suggest recurrence
• Short doubling time usually is predictor of occult metastasis

13. 2. Tumor marker for germ cell tumors of ovary and testis
• Embryonal carcinoma
• Malignant teratoma
3. Can also be increased in
• Pancreatic, gastric, bronchogenic and colon cancer
• Benign disease like hepatitis, post necrotic cirrhosis, primary biliary
cirrhosis.
4. Neonatal hepatitis and neonatal biliary atresia.
5. Screening for fetal defects and placental diseases

14. CARCINOMA EMBRYONIC ANTIGEN (CEA)
• High molecular weight glycoprotein
• Normal value is <2.5ng/ml
• Half life 3-13 days
• Has a diagnostic and prognostic importance in colorectal cancer
• Lacks high sensitivity and specificty

15. INTERPRETATION
In Colon cancer
• After complete removal of colon cancer, the levels should fall to
normal in 6-12 weeks.
• CEA has sensitivity of 97% in detecting recurrence in patients with
preoperative elevated levels
• Increase concentration indicates poor prognosis within a given
stage

16. • High level correlate with metastasis (80% patient of colon cancer
with level > 20 ng/ml have recurrence in 14 months)
• Concentrations < 5ng/ml before therapy correlate with localized
disease and good prognosis
• Uninterrupted increase denote failure to response
• Immediate sustained decrease followed by increase indicate, lack of
response

17. • Undifferentiated or poorly differentiated tumors do not produce
CEA
• Levels <2.5 ng/ml do not rule out primary, metastatic or recurrent
cancer
• Surge in CEA for weeks followed by decrease indicate response

18. Increased in
• Cancers of Stomach, Pancreas, Lung, Breast, Head and neck and
ovary
• Effusion fluids due to these cancers
• Active non malignant inflammatory diseases like UC, peptic ulcers,
regional enteritis, chronic pancreatitis
• Liver diseases, Renal failure, Heavy smokers

19. CA-125
• A mucin-like glycoprotein with a molecular weight of 200kDa
recognized by monoclonal antibody OC 125
• Normal value <35 U/ml
• Has a half -life of 3-5days
• Elevated in more than 80% of non-mucinous ovarian cancer

20. INTERPREATION
• Normal concentrations does not exclude tumor
• Not useful in distinguish benign and malignant pelvic mass
• Not recommended for screening women for serous carcinomas of ovary
• May be useful for screening in hereditary cancer syndrome
• Correlates with poorer prognosis if elevated 3-6 weeks after surgery

21. • Concentration of > 35 U/ml detects residual tumor in 95 % patients but
normal levels do not exclude
• Rising levels during chemotherapy is associated with tumor
progression and fall to normal is associated with response
• Rising concentration may precede clinical recurrence by many months
but normal levels does not indicate absence of persistent or recurrent
tumor
• Values > 65 U/ml correlate with peritoneal involvement

22. • Prognosis may be better if
1. 50% decline within 5 days of surgery
2. Ratio of postoperative and preoperative concentrations (4 weeks)
3. Ratio >0.1 to <0.5 may benefit from chemotherapy
4. Ratio > 0.8 should consider alternative therapy

23. Increased in
• Non mucinous epithelial ovarian carcinoma (85%) and Tumors of
Fallopian tube (100%)
• Cervical adenocarcinoma, Endometrial adenocarcinoma,
Trophoblastic tumors, liver, lung and pancreas
• Non hodgkin lymphomas representing pleuropericardial or peritoneal
involvement
• Cirrhosis, Renal failure, Menstruation, Endometriosis, disorders of
GI tract

24. HUMAN CHORIONIC GONADOTROPHIN
(hCG)
• A glycoprotein hormone synthesized by placenta
• Has alpha and beta subunits
• Normal value of beta hCG is<5mIU/ml
• Normal half-life of 12-20hrs

25. • Used as a routine pregnancy test
• Diagnosis and monitor course and evaluate prognosis of gestational
trophoblastic tumors (with AFP)
• Differentiation of ectopic pregnancy from other causes of acute
abdomen
• Prenatal screening of Down syndrome

26. • Increased levels after 12 weeks of pregnancy >500,000 IU/24 hours
usually are associated with moles and level >1,000,000 IU are alsmot
always associated with moles.
• In choriocarcinoma failure to fall to an undetectable level or a rise
after initial fall, signals residual tumor
• Also increased in non seminomatous germ cell tumors of testis, some
non trophoblastic cancer like ovary, GI tract, lung and breast.

27. PROSTATE SPECIFIC ANTIGEN (PSA)
• Also known as human kallikrein 3
• Serine protease produced by prostatic acinar cells
• Also by periurethral glands and breast in women, pancreas and
salivary glands in both sex
•
Reference rang <4ng/ml with half life of 4 days

28. INTERPRETATION
• Recommended for screening along with DRE
• Used in staging of prostate cancer
- < 4ng/ml, organ confined disease
- < 10ng/ml, bone metastasis is rare
- > 10ng/ml, >50% have extracapsular disease
- > 50ng/ml, most have positive lymphnodes
- >100ng/ml, predicts bone mets with 90% accuracy, S/S=66%/96%
with a PPV = 79%.

29. • Failure of radiation to decrease PSA to < 1ng/ml means likelihood of
recurrence
• After radical prostatectomy doubling time reflects aggressiveness of
original cancer
• Free PSA and complex PSA help in differentiating cancer from BPH
and prostatitis

31. PSA velocity and density
• More rapid rate of increase of velocity (>0.75 ng/ml/year or
>20%/year) correlates with cancer. Requires min. 3 tests/18 months.
• Specially useful when PSA levels are between 4-10ng/ml
• Low density is unlikely to be cancer (<0.15)

32. • DRE increases PSA significantly if initial value is >20ng/ml
• PSA has no circadian rhythm but variation can occur between
specimens collected on same day
• Ejaculation causes transient increase < 1.0 ng/ml for 48 hrs
• Slight increase may be associated with cancer of salivary gland, sweat
glands, breast, colon, lung and ovary and in conditions like ARF and
MI
• Indwelling catheters, vigorous bicycle exercise, Treadmill stress test

33. CA 19-9
• Blood group carbohydrate
• Sialylated derivative of Lewis antigen, and is denoted a Lexa
• Synthesized by normal human pancreatic and biliary ductal cells
• Also by gastric, colonic, endometrial and salivary epithelia
• Normal value <37 U/ml

34. INTERPRETATION
• Used in detection, diagnosis and prognosis of pancreatic cancer
• To determine preoperative resectability
• Only 5 % of patient with levels >1000 U/ml are surgically resectable
• Post surgical increase concentration correlates with recurrence
• May indicate development of Cholangiocarcinoma in PSC

35. CA 15-3
• Glycoprotein expressed by various adenocarcinoma especially
breast
• Half life of around 7 days
• Only to detect breast carcinoma recurrence and to monitor
response to treatment (FDA)

36. INTERPRETATION
• Increases directly related to stage of disease
• Increases in 75% with progressive disease
• Decreases in 38% responding to therapy
• >30 U/L indicates shorter survival
• Also increased in benign breast disease and liver disease

37. CA 72-4
• A high molecular weight (>106 Da) mucin-like complex
• Marker for carcinomas of the GI tract and of the ovary
• Also used in multivariate analysis of colorectal cancer with βhcg and
CEA for prognosis

38. NEXT SESSION
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39. THANK YOU