STEPTRACKERGENERAL PRINCIPLES | PATHOLOGY | HIGH-YIELD REVIEW

Tumor Markers & IHC Stains

Serum markers follow a tumor's burden; immunostains tell the pathologist what a cell actually is.

FOCUS ON
Serum markers are best for monitoring treatment and recurrence, not screening or diagnosis; biopsy confirms. Know each marker's common false positives. For IHC, the intermediate filaments sort tumors by lineage: keratin (epithelium), vimentin (mesenchyme), desmin (muscle), GFAP (glia), neurofilament (neurons).
SERUM MARKER
TUMOR(S)
BEST USE
ALSO RAISED IN
PSA
Prostate adenocarcinoma
Monitoring; screening only by shared decision
BPH, prostatitis
CEA
Colorectal, pancreatic, gastric, breast, medullary thyroid
Recurrence after colon resection
Smokers, IBD, pancreatitis
AFP
Hepatocellular carcinoma, yolk sac tumor, mixed germ cell tumors
HCC surveillance with ultrasound; germ cell tumor follow-up
Pregnancy (↑ with neural tube defects), ataxia-telangiectasia, hepatitis
β-hCG
Choriocarcinoma, hydatidiform mole; some seminoma/dysgerminoma
Molar pregnancy follow-up
Pregnancy
CA-125
Ovarian epithelial (serous) carcinoma
Monitoring response and relapse
Endometriosis, PID, pregnancy, menstruation
CA 19-9
Pancreatic adenocarcinoma, cholangiocarcinoma
Monitoring
Biliary obstruction, pancreatitis
Calcitonin
Medullary thyroid carcinoma
Screening MEN2 families; follow-up
—
LDH · PLAP
Seminoma/dysgerminoma, lymphoma (LDH); seminoma (placental ALP)
Tumor burden
LDH: hemolysis, tissue injury
Thyroglobulin
Papillary and follicular thyroid carcinoma
Recurrence after total thyroidectomy
Any remaining thyroid tissue
Chromogranin A · urine 5-HIAA
Carcinoid / neuroendocrine tumors
Carcinoid syndrome workup
PPI use (chromogranin)
M-protein
Multiple myeloma, Waldenström, MGUS
Serum/urine electrophoresis, free light chains
—

Mechanism — marker as a tumor-burden gauge

Tumor cellsRelease protein
→
Serum levelTracks burden
→
FallsAfter resection/therapy
→
Rises againRecurrence
→
BiopsyConfirms

A raised marker alone never makes the diagnosis — tissue does.

Immunohistochemistry → lineage

STAIN
MARKS
Cytokeratin
Epithelium → carcinoma; also mesothelioma
Vimentin
Mesenchyme → sarcoma; also RCC, endometrial
Desmin
Muscle → leiomyo-, rhabdomyosarcoma
GFAP · neurofilament
Glial tumors · neuronal tumors
S-100 · HMB-45, Melan-A
Melanoma, schwannoma, Langerhans cells · melanoma
Chromogranin, synaptophysin
Neuroendocrine: small cell, carcinoid
CD45 · CD20 · CD3
Lymphoma · B cell · T cell
CD15, CD30
Reed-Sternberg cells (Hodgkin)
CD117 · CD31/CD34
GIST, mast cells · vascular tumors
TTF-1 · CDX2
Lung adenocarcinoma, thyroid · intestinal origin
Calretinin, WT-1
Mesothelioma
ER/PR, HER2 · PSA
Breast (guides therapy) · prostate

How it's tested

COMMON CONFUSIONCEA and CA-125 are poor screening tests. Their job is to show whether treatment worked and whether the cancer has returned.
THE TRAPAn undifferentiated metastasis of unknown origin: keratin⁺ means carcinoma, CD45⁺ means lymphoma, S-100⁺/HMB-45⁺ means melanoma. Then TTF-1, CDX2, PSA or ER point to the primary site.
YOUR APPROACHFor serum markers: tumor → marker → use → false positives. For stains: lineage first (filaments), then organ-specific markers.

If you see… think…

Young man, testicular mass, ↑ AFP and ↑ hCG → mixed nonseminomatous germ cell tumor
Boy under 3, testicular mass, AFP only → yolk sac tumor
CEA climbing 2 years after colectomy → colorectal recurrence
Very high hCG, uterus large for dates, "snowstorm" ultrasound → complete mole
Small blue cells, chromogranin⁺ and synaptophysin⁺ → small cell carcinoma
Gastric spindle-cell tumor, CD117⁺ → GIST
Pleural tumor, calretinin⁺, WT-1⁺ → mesothelioma
Pigmented skin tumor, S-100⁺, HMB-45⁺ → melanoma
Undifferentiated tumor, CD45⁺ → lymphoma
Raised CA-125 in a woman with endometriosis → false positive