In cancer biology, certain tumor cells behave much like stem cells – they can self-renew, resist therapy, and drive relapse or metastasis. These so-called circulating tumor cells (CTCs) or cancer stem cells (CSCs) are identified not by classic serum tumor markers (like PSA or CEA), but by specific cell-surface and transcriptional markers that reflect their stem-like potential.
Together, these markers define a subpopulation of cancer cells with heightened survival and regenerative capacity – a major target for research and therapy. The table below summarizes several of these key cancer stem-cell–associated tumor markers and their biological significance:
| Marker | What it is (category) | What positivity often suggests | Practical notes |
| VHL mut | Gene/tumor-suppressor mutation | Common in clear-cell renal cell carcinoma; also VHL syndrome tumors | Activates HIF/VEGF signaling; can predict biology and may relate to anti-VEGF sensitivity. |
| panCK | Cytokeratin cocktail (epithelial marker) | Carcinoma (epithelial origin) vs sarcoma/melanoma/lymphoma | One of the first stains to confirm “this is an epithelial cancer.” |
| EpCAM / EpCAm+ve | Epithelial cell adhesion molecule (surface) | Many adenocarcinomas (colon, breast, ovary, etc.) and circulating tumor cells (CTCs) | Helps confirm epithelial origin; widely used to capture CTCs. |
| MUC-1 | Mucin glycoprotein (surface) | Adenocarcinomas (breast, pancreas, ovary, lung) | Overexpression may reflect aggressive/EMT features; therapeutic antibodies exist in trials. |
| PSMA | Prostate-specific membrane antigen | Prostate adenocarcinoma; also expressed on tumor neovasculature in other cancers | Key for PSMA-PET imaging/Lu-177-PSMA therapy in prostate cancer. Not fully prostate-exclusive. |
| c-MET (MET) | Receptor tyrosine kinase | Overexpressed/amplified in lung, gastric, HCC and others | Protein positivity ≠ mutation; MET exon 14 skipping/amplification are drug-targetable (capmatinib/tepotinib, etc.). |
| CD31 | Endothelial marker (PECAM-1) | Vascular/endothelial origin (angiosarcoma, hemangiomas); highlights blood vessels | Used to assess angiogenesis or vascular invasion. |
| CD34 | Hematopoietic progenitor & endothelial marker | Vascular tumors, some GIST, dermatofibrosarcoma protuberans | Often co-stained with CD31; also marks fibroblastic tumors. |
| CD99 | MIC2 surface protein | Ewing sarcoma/PNET; T-ALL; some others | Strong membranous CD99 supports Ewing in the right context but is not specific. |
| CD19 | B-cell antigen | B-cell lymphomas/leukemias | If a solid mass is CD19+, think hematolymphoid rather than carcinoma. |
| CD44 | Adhesion receptor (hyaluronan receptor) | Widespread; linked to EMT, invasion, “stem-like” phenotype in many tumors | Often paired with CD24, CD133 in “cancer stem cell” panels. |
| CD133 (PROM1) | Stem/progenitor cell marker | “Cancer stem cell” subpopulations in glioma, colon, ovarian, etc. | Correlates with resistance/relapse risk in some studies; mainly research/stratification. |
| Nanog | Pluripotency transcription factor | “Stem-like” signatures across tumors | Research/IHC marker; indicates de-differentiation potential. |
| OCT4 (often miswritten as OKT-4) | Pluripotency TF (POU5F1) | Germ cell tumors (seminoma/dysgerminoma), pluripotent signatures | Check spelling: OCT4 is tumor marker; OKT-4 is an antibody name for CD4 (unrelated). |
| SOX-2 | Pluripotency TF | Squamous cell carcinomas, gliomas, stem-like features | Diagnostic in some settings; can indicate poor differentiation. |
| CD63 | Tetraspanin/exosome marker | Exosomes, platelet/immune granules; variably on tumors | Used in exosome assays; not tumor-specific by itself. |
How to read these together
- Carcinoma panel: panCK+, EpCAM+, often MUC-1+ → supports epithelial/adenocarcinoma origin.
- Vascular origin: CD31+ and CD34+ (± ERG) → endothelial/angiosarcoma or rich neovasculature.
- Hematolymphoid: CD19+ suggests B-cell process (lymphoma/leukemia), not a typical solid carcinoma.
- Stemness/aggressiveness: CD133/CD44/Nanog/OCT4/SOX2 co-positivity flags stem-like/EMT biology (often tied to therapy resistance/recurrence risk) but is not diagnostic alone.
- Organ-specific clues: PSMA points to prostate origin or tumor neovasculature; c-MET overexpression may prompt molecular testing to see if a targetable MET alteration exists.
- VHL mutation specifically pushes the differential toward clear-cell RCC biology (even in metastases), with implications for VEGF-axis therapies.
