How tumor markers are tested on Step 1
Expect a tumor with a lab value or stain and a question about the pairing, or a marker that is elevated for a benign reason. A common trap is choosing a marker to screen or diagnose when its role is to follow treatment.
A falling marker after surgery means the tumor was removed; a rising marker during follow-up signals recurrence. Diagnosis almost always requires tissue.
Serum tumor markers
Most serum markers are oncofetal proteins, hormones, or glycoproteins shed by tumor cells.
| Marker | Main tumors | Also elevated in (non-cancer) |
|---|---|---|
| AFP (α-fetoprotein) | Hepatocellular carcinoma; yolk sac (endodermal sinus) tumor; mixed germ-cell tumors | Pregnancy, neural tube defects (fetal), cirrhosis, hepatitis |
| β-hCG | Choriocarcinoma, hydatidiform mole, some seminomas and mixed germ-cell tumors | Normal pregnancy |
| CEA | Colorectal and pancreatic carcinoma; also gastric, breast, lung, medullary thyroid | Smoking, inflammatory bowel disease, pancreatitis, cirrhosis |
| CA-125 | Epithelial ovarian carcinoma | Endometriosis, pelvic inflammatory disease, pregnancy, menstruation |
| CA 19-9 | Pancreatic adenocarcinoma; cholangiocarcinoma | Pancreatitis, biliary obstruction |
| CA 15-3 / CA 27-29 | Breast carcinoma (monitoring) | Benign breast and liver disease |
| PSA | Prostate adenocarcinoma | Benign prostatic hyperplasia, prostatitis, recent ejaculation or instrumentation |
| Calcitonin | Medullary thyroid carcinoma (parafollicular C cells) | — |
| Alkaline phosphatase | Bone metastases, liver metastases | Paget disease of bone, cholestasis, growth |
Markers in the right column explain many false positives — and why markers are poor screening tools.
Immunohistochemistry: what stains which tissue
When a tumor is poorly differentiated, stains for intermediate filaments and lineage proteins reveal its origin — and therefore its treatment.
| Stain | Identifies | Classic tumors |
|---|---|---|
| Cytokeratin | Epithelial cells | Carcinomas, mesothelioma |
| Vimentin | Mesenchymal cells | Sarcomas, also renal cell carcinoma, endometrial carcinoma |
| Desmin | Muscle | Leiomyosarcoma, rhabdomyosarcoma |
| GFAP | Glial cells | Astrocytoma, glioblastoma |
| S-100 | Neural crest | Melanoma, schwannoma, Langerhans cell histiocytosis |
| Chromogranin, synaptophysin | Neuroendocrine cells | Carcinoid, small cell lung carcinoma, pheochromocytoma |
| PSA | Prostate epithelium | Metastatic prostate adenocarcinoma |
| TRAP | Tartrate-resistant acid phosphatase | Hairy cell leukemia |
| CD markers | Hematopoietic lineage | CD20 (B cells), CD3 (T cells), CD15/CD30 (Reed-Sternberg cells), CD117 (GIST) |
Lineage stains are often combined: a cytokeratin-positive, vimentin-negative tumor is a carcinoma.
Uses and limits
The value of a marker depends on what question it is answering.
CA-125 is not a screening test for ovarian cancer in average-risk women, and CEA is not a screening test for colorectal cancer — colonoscopy is. Both are used after diagnosis to follow treatment.
Putting it together
Most questions give a clinical picture first; the marker confirms what the picture suggests.
A 25-year-old man has a painless testicular mass. Orchiectomy shows a germ-cell tumor; serum AFP is markedly elevated. The pathologist initially reported a pure seminoma. What does the AFP imply?
- Pure seminomas do not produce AFP (they may produce modest β-hCG).
- AFP is produced by yolk sac elements.
- An elevated AFP therefore means the tumor contains a nonseminomatous component, even if the sampled sections looked like seminoma.
Answer. The tumor must be treated as a nonseminomatous (mixed) germ-cell tumor, which changes staging and management. AFP and β-hCG are then followed to monitor treatment and detect relapse.
- Hepatocellular carcinoma in a patient with cirrhosis → AFP.
- Very high β-hCG with hemoptysis and a recent pregnancy → choriocarcinoma.
- Painless jaundice, weight loss → CA 19-9 (pancreatic head).
- Thyroid nodule with amyloid stroma → calcitonin (medullary carcinoma, MEN 2).