Journal Article

Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus

Wardzala, Jacek, DoRosario, Andrew, Kupper, Thomas S., Wang, Linda C., Rodig, Scott J., DeCaprio, James A., Barletta, Justine A., Holloway, Dustin T., Scanlon, Jessica J., Martinez-Fernandez, Alejandro, Cooper, Dylan J., Bellizzi, Andrew M., Sadasivam, Subhashini, Cheng, Jingwei, Laga, Alvaro C.

2012

Overview

A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.

• Publisher: American Society for Clinical Investigation
• Subject: Aged / Aged, 80 and over / Amino acid substitution / Antibodies, Viral - immunology / Antigens / Antigens, Polyomavirus Transforming - immunology / Antigens, Polyomavirus Transforming - metabolism / Biomedical research / Carcinoma / Carcinoma, Merkel Cell - diagnosis / Carcinoma, Merkel Cell - metabolism / Carcinoma, Merkel Cell - virology / Care and treatment / Cell Line, Tumor / Chromosomes / Diagnosis / DNA Mutational Analysis / Female / Gene Dosage / Gene mutations / Genes, Tumor Suppressor / Genetic aspects / Genomes / Genotype / Humans / Identification and classification / Immunohistochemistry / Integration / Male / Merkel cell carcinoma / Merkel cell polyomavirus - genetics / Merkel cell polyomavirus - immunology / Merkel cell polyomavirus - metabolism / Metastasis / Middle Aged / Molecular Diagnostic Techniques / Monoclonal antibodies / Mutation / Neuroendocrine tumors / Oncogenes / p53 protein / Patients / Polymerase chain reaction / Polyoma virus / Polyomavirus / Polyomavirus Infections - diagnosis / Polyomavirus Infections - metabolism / Polyomavirus Infections - virology / Primers / Properties / Real-Time Polymerase Chain Reaction / Tumor Virus Infections - diagnosis / Tumor Virus Infections - metabolism / Tumor Virus Infections - virology / Tumors