title: Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus.
abstract: 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.
authors.affiliation: Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.forename: Jingwei
authors.initials: J
authors.lastname: Cheng
authors.forename: Jacek
authors.initials: J
authors.lastname: Wardzala
authors.forename: Andrew
authors.initials: A
authors.lastname: DoRosario
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Scanlon
authors.forename: Alvaro C
authors.initials: AC
authors.lastname: Laga
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martinez-Fernandez
authors.forename: Justine A
authors.initials: JA
authors.lastname: Barletta
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Bellizzi
authors.forename: Subhashini
authors.initials: S
authors.lastname: Sadasivam
authors.forename: Dustin T
authors.initials: DT
authors.lastname: Holloway
authors.forename: Dylan J
authors.initials: DJ
authors.lastname: Cooper
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
authors.forename: Linda C
authors.initials: LC
authors.lastname: Wang
authors.forename: James A
authors.initials: JA
authors.lastname: DeCaprio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000276:immunology; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000175:diagnosis / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059965:Merkel cell polyomavirus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009857:Oncogenes; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000378:metabolism / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000378:metabolism / Q000821:virology*
chemical_list: D000914:Antibodies, Viral; D000952:Antigens, Polyomavirus Transforming