A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

AIMS: Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective. METHODS AND RESULTS: Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches. CONCLUSIONS: The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma.

Strong Annexin A10 Expression Supports a Pancreatic Primary and Combined Annexin A10, Claudin 18, and SOX2 Expression Supports an Esophagogastric Origin in Carcinomas of Unknown Primary.

Primary tumor site determination for gastrointestinal (GI) tract and pancreaticobiliary (PB) tree carcinomas that present as metastasis of unknown primary can be problematic. Annexin A10 (ANXA10), claudin 18 (CLDN18), and trefoil factor 1 (TFF1) have been identified through expression profiling as markers of gastric lineage commitment; sex-determining region Y (SRY)-box transcription factor 2 (SOX2) expression has been reported in several tumor types, including gastric adenocarcinomas. We evaluated the diagnostic utility of immunohistochemistry for ANXA10, CLDN18, SOX2, and TFF1 for determining the site of origin for GI/PB adenocarcinomas. Immunohistochemistry for all 4 markers was performed on tissue microarrays including 559 GI/PB tumors and 421 other tumors. H-scores were calculated as the product of the intensity (0 to 3) and extent (percentage, 0% to 100%) of staining. Positive staining was defined as >5% staining. ANXA10 expression was most frequent in pancreatic adenocarcinomas when compared with all other GI/PB tumors (96.4% vs. 43.5%, P <0.001). Strong staining for ANXA10 (H-score ≥200) distinguished pancreatic ductal adenocarcinoma from intrahepatic cholangiocarcinoma and adenocarcinomas of the gallbladder and colorectum (69.6% vs. 0%, P <0.001). Triple positivity for ANXA10, CLDN18, and SOX2 was more frequent in esophagogastric tumors than in other GI/PB tumors (22.6% vs. 4.1%; P <0.001). TFF1 expression was observed in nearly all tumor types. Staining for ANXA10, CLDN18, and SOX2 as part of a panel may aid in distinguishing esophagogastric adenocarcinomas from lower GI/PB tumors. ANXA10 staining may be particularly useful in distinguishing pancreatic adenocarcinomas from intrahepatic cholangiocarcinoma and adenocarcinomas of the gallbladder and colorectum.