Tumour Markers

Definition

Biochemical substances from tumour cells, detectable in blood/fluid. NOT for primary diagnosis (also made by normal cells → ↓sensitivity+↓specificity). Uses: (1) adjunct to pathologic diagnosis, (2) prognosis/monitoring therapy — disappears after resection, reappearance = recurrence.

Classification + examples

Oncofoetal antigens

AFP — hepatocellular Ca, non-seminomatous testicular germ cell tumour. Also ↑ in hepatitis/cirrhosis/toxic liver injury/pregnancy.
CEA — GIT/pancreas/breast Ca. Also ↑ in UC, Crohn’s, hepatitis, chronic bronchitis.

Hormones

hCG — choriocarcinoma, germ cell tumours
Calcitonin — medullary thyroid Ca
Catecholamines/VMA — phaeochromocytoma, neuroblastoma

Enzymes

PSA — prostate Ca. Classic ↓sensitivity(normal PSA+cancer)+↓specificity(↑in BPH) example; real value = post-treatment recurrence detection, not screening.
PLAP — seminoma
NSE — neuroblastoma, small cell lung Ca
LDH — germ cell tumours, lymphoma (burden/prognostic)

Cancer antigens (mucin/glycoprotein)

CA-125 — ovary, fallopian tube, colon
CA19-9 — pancreas, GI/hepatobiliary, ovary
CA15-3 — breast

Cell-surface/cytoplasmic proteins — paraproteins (Bence-Jones in myeloma); surface antigens more for flow cytometry/IHC than serum assay.

Molecular extensions

Diagnosis: PCR clonal TCR/Ig gene rearrangement (monoclonal=neoplastic vs polyclonal=reactive); FISH/PCR translocations (Ewing sarcoma, leukaemias/lymphomas); BCR-ABL PCR→CML; JAK2 mutation→polycythaemia vera. Prognosis: HER2 amplification(breast), MYCN amplification(neuroblastoma), TP53 mutation(poor prognosis, multiple cancers). Minimal residual disease: BCR-ABL PCR quantification(CML); liquid biopsy (circulating tumour cells/cell-free tumour DNA).

Clinical relevance

PSA = teaching example of marker limitation (low sens+spec) yet genuine post-Tx surveillance value. “Disappears after resection, reappears=recurrence” = most testable general rule. Non-neoplastic elevations (AFP/CEA/CA-125/CA19-9/CA15-3) → never diagnose cancer on marker alone. Liquid biopsy/MRD PCR = direction field is heading (continuous molecular monitoring vs single static value).

Definition and General Principles

Tumour markers are biochemical substances — produced by tumour cells and detectable in blood or other body fluids — used as an adjunct to pathological cancer diagnosis. They differ fundamentally from histological or cytological methods: rather than staining and examining the tumour cells themselves, a tumour marker measures a soluble product the tumour elaborates.

A critical limitation applies to nearly every tumour marker: most of these substances are also produced, in smaller quantity, by normal cells. Serum measurement therefore reflects the total circulating substance, not tumour output alone, giving markers characteristically low sensitivity and low specificity. Because of this, tumour markers are used for two purposes only:

As an adjunct to a pathological diagnosis already reached by other means — never as the primary basis for diagnosing cancer.
For prognosis and monitoring therapy — following a marker’s level over time is far more clinically useful than a single measurement, since successful tumour resection causes the marker to disappear from serum, and its reappearance almost always signals recurrence.

Classification of Tumour Markers

Tumour markers are grouped by their biochemical nature: oncofoetal antigens, hormones, enzymes, cancer antigens (mucins/glycoproteins), and cell-surface/cytoplasmic proteins.

Oncofoetal Antigens

Substances normally synthesised by foetal tissue, re-expressed by certain tumours in adult life.

Alpha-foetoprotein (AFP) — glycoprotein normally made by foetal liver cells. Elevated in hepatocellular carcinoma and non-seminomatous germ cell tumours of the testis. Also elevated in several non-neoplastic conditions — hepatitis, cirrhosis, toxic liver injury, and normal pregnancy — a reminder that no tumour marker is cancer-specific.
Carcinoembryonic antigen (CEA) — glycoprotein normally synthesised in embryonic gut, pancreas, and liver tissue. Elevated in carcinomas of the gastrointestinal tract, pancreas, and breast. Also elevated in non-neoplastic conditions — ulcerative colitis, Crohn’s disease, hepatitis, chronic bronchitis.

Hormones

Tumours of endocrine or endocrine-related origin, or tumours with ectopic hormone production, elaborate detectable hormones:

Human chorionic gonadotropin (hCG) — choriocarcinoma, germ cell tumours.
Calcitonin — medullary carcinoma of the thyroid.
Catecholamines and their metabolite VMA (vanillylmandelic acid) — phaeochromocytoma, neuroblastoma.

Enzymes

Prostate-specific antigen (PSA) — one of the most widely used tumour markers in clinical practice, raised in prostatic carcinoma. Like every other marker, it illustrates the general problem well: PSA is also elevated in benign prostatic hyperplasia (low specificity), and prostate cancer can be present with a normal PSA (low sensitivity) — its use as a population screening tool is consequently controversial. Its real clinical strength is detecting residual disease or recurrence after treatment, where a rising PSA in a post-treatment patient is highly informative.
Placental alkaline phosphatase (PLAP) — seminoma.
Neuron-specific enolase (NSE) — neuroblastoma, small cell carcinoma of lung.
Lactate dehydrogenase (LDH) — germ cell tumours, lymphoma (used as a prognostic/tumour-burden marker rather than diagnostic).

Cancer Antigens (Mucin/Glycoprotein Markers)

CA-125 — cancers of the ovary, fallopian tube, and colon.
CA 19-9 — cancers of the pancreas, gastrointestinal and hepatobiliary tract, and ovary.
CA 15-3 — breast carcinoma.

Like AFP and CEA, these mucin-type antigens can all be elevated in a variety of non-neoplastic conditions and therefore also lack the sensitivity/specificity required for early cancer detection — their principal clinical use is again monitoring an already-diagnosed cancer.

Cell-Surface Antigens and Cytoplasmic Proteins

Includes immunoglobulins/paraproteins (e.g. Bence-Jones protein in multiple myeloma) and cell-surface antigens used more in immunophenotyping (flow cytometry, immunohistochemistry) than as serum assays — these overlap with the modern diagnostic aids described below.

Modern Molecular Extensions of Tumour Marker Testing

Beyond classical biochemical assays, molecular techniques now serve overlapping diagnostic, prognostic, and monitoring roles:

Diagnosis of malignancy — PCR-based detection of clonally rearranged T-cell receptor or immunoglobulin genes distinguishes a monoclonal (neoplastic) lymphoid proliferation from a polyclonal (reactive) one. Specific translocations define particular haematopoietic neoplasms and some solid tumours — FISH or PCR detects the translocation characteristic of Ewing sarcoma or various leukaemias/lymphomas, and PCR-based detection of the BCR-ABL transcript confirms chronic myeloid leukaemia. Some malignancies are now defined by specific point mutations — e.g. JAK2 mutation in polycythaemia vera.
Prognosis and behaviour prediction — FISH/PCR detection of oncogene amplification (HER2 in breast cancer, MYCN in neuroblastoma) carries direct therapeutic and prognostic weight; genome sequencing detects point mutations such as TP53, associated with poor outcome across many cancer types.
Detection of minimal residual disease — PCR quantification of BCR-ABL transcripts tracks residual disease in treated CML. The recognition that advanced tumours shed both intact circulating tumour cells and cell-free circulating tumour DNA has driven interest in “liquid biopsy” blood tests that follow tumour burden non-invasively.

Clinical Relevance

The PSA story is the clearest teaching example of why no tumour marker can be used alone for screening: it demonstrates simultaneously low sensitivity (cancer with normal PSA) and low specificity (elevated PSA in benign hyperplasia), yet remains genuinely valuable for a different purpose — post-treatment surveillance, where the pre-treatment baseline is already known and a rise from that baseline is the signal being sought.
The rule “a marker disappearing after resection and reappearing later signals recurrence” is the single most examination-relevant clinical application of tumour markers as a group, more testable than any individual marker-tumour pairing.
Recognising that oncofoetal antigens (AFP, CEA) and cancer antigens (CA-125, CA19-9, CA15-3) are also elevated in specific non-malignant conditions prevents the common error of treating an elevated marker as diagnostic proof of cancer in isolation from clinical and pathological correlation.
Liquid biopsy and minimal-residual-disease PCR monitoring represent the direction classical tumour marker testing is evolving toward — from a single static blood value to a continuously monitored, tumour-specific molecular signal.

No Rendered Diagram for This Topic

Tumour Markers is a classification-and-list topic — a set of biochemical substances grouped by chemical class and matched to the tumours that elevate them — rather than a multi-step pathogenic mechanism. There is no genuine sequential or branching process here that a flowchart would clarify beyond what the classification table in notes.md already communicates; forcing a diagram onto a list would add visual complexity without adding understanding.

Hand-draw suggestion (optional, not a rendered requirement): a simple two-column revision table — marker name in one column, associated tumour(s) plus the key non-neoplastic condition(s) that also raise it in the other — is the most efficient hand-drawn aid for this topic, more useful for rapid recall than any flowchart would be.