Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas Journal Article


Authors: Busam, K. J.; Jungbluth, A. A.; Rekhtman, N.; Coit, D.; Pulitzer, M.; Bini, J.; Arora, R.; Hanson, N. C.; Tassello, J. A.; Frosina, D.; Moore, P.; Chang, Y.
Article Title: Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas
Abstract: Merkel cell carcinoma (MCC) is the eponym for primary cutaneous neuroendocrine carcinoma. Recently, a new polyoma virus has been identified that is clonally integrated in the genome of the majority of MCCs, with truncating mutations in the viral large T antigen gene. We examined the presence of Merkel cell polyomavirus (MCV) in a set of 17 frozen tumor samples by quantitative polymerase chain reaction; 15 of them (88%) were positive. Sections from corresponding archival material were analyzed by immunohistochemistry (IHC) with the novel monoclonal antibody CM2B4, generated against a predicted antigenic epitope on the MCV T antigen, and tested for the expression of cytokeratin 20 (CK20). Sufficient archival material for IHC was available in only 15 of the 17 cases whose frozen tissue samples had been studied by polymerase chain reaction. Of the 15 tumors analyzed immunohistochemically, 10 (67%) showed positive labeling with CM2B4, 14 (93%) expressed CK20. A tissue microarray of 36 MCCs, 7 combined squamous and neuroendocrine carcinomas of the skin, and 26 pulmonary neuroendocrine carcinomas were also examined by IHC. Of the 36 MCCs assembled on a microarray, 32 (89%) tumors expressed CK20, and 27 (75%) were immunoreactive with CM2B4. The skin tumors with a combined squamous and neuroendocrine phenotype and all pulmonary neuroendocrine carcinomas failed to react with CM2B4. Our study shows that CM2B4 is a useful reagent for the diagnosis of MCC. It labels the majority of MCCs, but fails to react with pulmonary neuroendocrine carcinomas. We also found that neuroendocrine carcinomas of the skin arising in association with a squamous cell carcinoma seem to be independent of MCV. Copyright © 2009 by Lippincott Williams & Wilkins.
Keywords: immunohistochemistry; adult; clinical article; human tissue; protein expression; aged; aged, 80 and over; middle aged; squamous cell carcinoma; carcinoma, squamous cell; cancer diagnosis; lymph nodes; polymerase chain reaction; phenotype; skin neoplasms; lung neoplasms; tumor markers, biological; immunoreactivity; skin carcinoma; monoclonal antibody; neuroendocrine tumor; skin tumor; quantitative analysis; dna, neoplasm; merkel cell carcinoma; merkel cell polyomavirus; cytokeratin 20; virus antigen; genome; lung carcinoma; mean corpuscular volume; merkel cell tumor; mixed tumor; polyoma virus; carcinoma, merkel cell; cell count; dna, viral; fluorescent antibody technique, direct; keratin-20; polyomavirus; polyomavirus infections; tissue array analysis; tumor virus infections
Journal Title: American Journal of Surgical Pathology
Volume: 33
Issue: 9
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2009-09-01
Start Page: 1378
End Page: 1385
Language: English
DOI: 10.1097/PAS.0b013e3181aa30a5
PUBMED: 19609205
PROVIDER: scopus
PMCID: PMC2932664
DOI/URL:
Notes: --- - "Cited By (since 1996): 20" - "Export Date: 30 November 2010" - "CODEN: AJSPD" - "Source: Scopus"
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MSK Authors
  1. Natasha Rekhtman
    424 Rekhtman
  2. Melissa P Pulitzer
    203 Pulitzer
  3. Daniel Coit
    542 Coit
  4. Achim Jungbluth
    454 Jungbluth
  5. Klaus J Busam
    688 Busam
  6. Denise Frosina
    123 Frosina
  7. Nicole C Hanson
    11 Hanson
  8. Jason Michael Bini
    3 Bini