Cite this page: Pernick N. Carcinoma of unknown primary. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainstissueoforigin.html. Accessed June 2nd, 2023.
Definition / general
- 3-5% of cancer diagnoses
- Choice of marker depends on what tumors are logically within the differential diagnosis
- Molecular products must be validated to show adequate performance characteristics for clinical use (Arch Pathol Lab Med 2010;134:216)
- Analysis may be affected by tumor heterogeneity (Genome Med 2013;5:29)
- Tumors of unknown primaries, even when accurately classified by molecular methods, may harbour molecular/genetic traits distinct from tumors of known primaries, and have poorer response to treatment (Cancer Treat Rev 2009;35:221)
- Immunohistochemistry profiles:
- Carcinoma of unknown primary, 18 markers (MD Anderson): table, Gastrointest Cancer Res 2007;1:229
- Adenocarcinoma, 12 markers + PCR (Turin, Italy): algorithm, J Transl Med 2012;10:12
- Adenocarcinoma, 15 markers (Tokyo, Japan): algorithm, PLoS One 2012;7:e31181
- Gene expression assays:
- Measures expression of up to thousands of genes simultaneously to identify those whose expression has changed compared to baseline (normal) levels
- Adenocarcinoma (Amsterdam): J Clin Oncol 2008;26:4435
- Carcinoma of unknown primary determined using Pathwork Tissue of Origin Test: Am J Surg Pathol 2013;37:1067, Diagn Pathol 2010;5:26
- Test also works on body fluid specimens: Cancer Cytopathol 2012;120:62
- Test may soon be offered by Response Genetics
- Poorly differentiated / undifferentiated tumors-1550 gene expression profile (The Methodist Hospital): J Clin Oncol 2009;27:2503
- Carcinoma of unknown primary determined using microarray reference database (Helsinki, Finland): Genome Med 2011;3:63
- Hybrid using IHC and gene expression assays:
- Carcinoma of unknown primary (Moffitt Cancer Center): J Mol Diagn 2010;12:476
- RT-PCR:
- RT-PCR (bioTheranostics): Oncologist 2010;15:500, J Clin Oncol 2013;31:217
- Computational:
- Computational strategy using high-throughput sequencing (ISOLATE): Bioinformatics 2009;25:2882
- MicroRNA based PCR methods:
- Rosetta Genomics: Oncologist 2012;17:801, Mol Cancer 2013;12:57
- CNS metastases (Heidelberg, Germany): Oncologist 2011;16:165
- 47 miRNA signature (Ferrara, Italy): J Pathol 2011;225:43
- 48 miRNA signature (MD Anderson) Clin Cancer Res 2011;17:4063
Recommended IHC markers
- Epithelial markers: low molecular weight keratin (CAM 5.2), AE1-AE3 cytokeratin cocktail, CK7, CK20, CEA and EMA
- Alternative epithelial markers on sarcomatoid carcinoma include p63, MOC-31 and TTF1 (Mod Pathol 2005;18:1471)
- Melanocytic markers: S100 (also a mesenchymal marker), HMB45, MelanA / Mart1
- Lymphoid markers: CD3 (T cells), CD20 (B cells), CD15 (Hodgkin), CD30 (Hodgkin & other) and various others
- Histiocytic markers: CD68, lysozyme, CD1a (Langerhans cells)
- Neuroendocrine markers: neuron specific enolase, chromogranin, synaptophysin, CD56 and CD57
- Mesenchymal markers: vimentin (non-specific), factor XIIIa (fibrous histiocytoma), factor VIII (vessels), CD31 (vessels), CD34 (vessels), D2-40 (lymphatics), HHF35 (actin), smooth muscle actin and desmin
- Cell proliferation / apoptosis markers: Ki-67, bcl2