Write a short note on tumour markers — types, clinical uses and limitations.
Definition
Tumour markers are substances produced by tumour cells, or by the host in response to a tumour, which can be measured in blood, urine or tissue and used to support diagnosis, assess prognosis, monitor treatment and detect recurrence. They may be oncofetal antigens, hormones, enzymes, glycoproteins or receptors.
Properties of an Ideal Tumour Marker
High sensitivity and specificity, produced only by malignant tissue, organ-specific, level proportional to tumour burden, detectable at an early stage, cheap and reproducible. No existing marker fulfils all these criteria — which is the key limitation to state in any answer.
Important Tumour Markers
| Marker | Principal Malignancy | Other Causes of Elevation |
|---|---|---|
| AFP (alpha-fetoprotein) | Hepatocellular carcinoma; non-seminomatous germ cell tumour | Cirrhosis, hepatitis, pregnancy, neural tube defects |
| CEA (carcinoembryonic antigen) | Colorectal carcinoma | Smoking, pancreatitis, IBD, cirrhosis, gastric and breast cancer |
| CA 19-9 | Pancreatic carcinoma; cholangiocarcinoma | Cholangitis, obstructive jaundice, pancreatitis |
| CA 125 | Epithelial ovarian carcinoma | Endometriosis, pelvic inflammatory disease, cirrhosis with ascites, menstruation, pregnancy, TB peritonitis |
| CA 15-3 / CA 27.29 | Breast carcinoma (monitoring) | Benign breast disease, liver disease |
| PSA (prostate-specific antigen) | Carcinoma prostate | Benign prostatic hyperplasia, prostatitis, catheterisation, digital rectal examination, cycling |
| beta-hCG | Choriocarcinoma, gestational trophoblastic disease, germ cell tumour | Pregnancy, hypogonadism |
| Calcitonin | Medullary carcinoma thyroid | Renal failure, MEN 2 screening |
| Thyroglobulin | Differentiated (papillary/follicular) thyroid carcinoma — follow-up | Thyroiditis, Graves' disease |
| LDH | Lymphoma, germ cell tumour (prognostic) | Haemolysis, hepatitis, myocardial infarction |
| Chromogranin A | Neuroendocrine tumours, carcinoid | Proton pump inhibitor use, renal failure |
| Urinary 5-HIAA | Carcinoid syndrome | Banana, pineapple, walnut ingestion |
| Beta-2 microglobulin | Multiple myeloma (prognostic, part of ISS staging) | Renal failure, lymphoma |
| Urinary VMA / metanephrines | Phaeochromocytoma, neuroblastoma | Stress, certain drugs and foods |
Clinical Uses
- Screening: very limited, because of poor specificity. Accepted uses are AFP with ultrasound for surveillance of cirrhotic patients for hepatocellular carcinoma, and calcitonin screening in MEN 2 families. PSA screening remains controversial and is offered only after discussion of risks and benefits.
- Diagnosis: supportive but rarely diagnostic alone — histopathology remains the gold standard. An exception is HCC, which may be diagnosed on characteristic imaging with a markedly raised AFP in a cirrhotic liver.
- Prognosis and staging: LDH and beta-2 microglobulin in lymphoma and myeloma; AFP, hCG and LDH determine risk group in germ cell tumours.
- Monitoring treatment response: the strongest use — a falling level indicates response, and the rate of fall (e.g. hCG half-life in germ cell tumour) predicts outcome.
- Detecting recurrence: a rising marker often precedes clinical or radiological relapse by months, as with CEA after colorectal resection and thyroglobulin after thyroidectomy.
The single most important line to write is that tumour markers are used mainly for MONITORING, not for screening or diagnosis, because both false positives (benign disease) and false negatives (poorly differentiated tumours that fail to secrete) are common.
Limitations
Elevated levels occur in many benign conditions; normal levels do not exclude malignancy; results vary between assay platforms, so serial measurements should use the same laboratory; and the hook effect may give falsely low readings when marker concentration is extremely high, as with hCG in choriocarcinoma.
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