Select Immunohistochemical Stains Useful in the Diagnosis of CUPS | |
| LIKELY PRIMARY PROFILE | COMMONLY CONSIDERED IHC TO ASSIST IN DIFFERENTIAL DIAGNOSIS OF CUPSa |
|---|---|
| Breast | ER, GCDFP-15, mammaglobin, Her-2/neu, GATA3 |
| Ovarian/mullerian | ER, WT1 gene, CK7, PAX8, PAX2 |
| Lung adenocarcinoma | TTF-1; nuclear staining, napsin A, SP-A1 |
| Germ cell | β-HCG, AFP, OCT3/4, CKIT, CD30 (embryonal), SALL4 |
| Prostate | PSA, α-methylacyl CoA racemase/P504S (AMACR/P504S), P501S (prostein), and PSMA, NKX3-1 |
| Intestinal | CK7, CK20, CDX-2, CEA |
| Neuroendocrine | Chromogranin, synaptophysin, CD56 |
| Sarcoma | Desmin (desmoid tumors), factor VIII (angiosarcomas), CD31, smooth muscle actin (leiomyosarcoma), MyoD1 (rhabdomyosarcoma) |
| Renal | RCC, CD10, PAX8, CD10 |
| Hepatocellular carcinoma | Hep Par-1, Arg-1, glypican-3 |
| Melanoma | S100, SOX-10, vimentin, HMB-45, tyrosinase and melan-A |
| Urothelial | CK7, CK20, thrombomodulin, uroplakin III |
| Mesothelioma | Calretinin, WT1, D2-40, mesothelin |
| Lymphoma | LCA, CD3, CD4, CD5, CD20, CD45 |
| SCC | p63, p40 (lung SCC), CK5/6 |
a Patterns emerging from coexpression of stains are better than individual stains to suggest putative primary site. Even with optimization, no IHC panel is 100% sensitive or specific (e.g., ovarian mucinous carcinoma can exhibit positivity with intestinal markers).
Abbreviations: AFP, α fetoprotein; Arg-1, arginase-1; β-hCG, β-human chorionic gonadotropin; CEA, carcinoembryonic antigen; CUPS, cancer of unknown primary site; ER, estrogen receptor; GCDFP-15, gross cystic disease fibrous protein-15; IHC, immunohistochemistry; LCA, leukocyte common antigen; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen; SCC, squamous cell carcinoma; SP-A1, surfactant protein A precursor; TTF, thyroid transcription factor; WT, Wilms' tumor.