title: Detection of Merkel cell polyomavirus in formalin-fixed, paraffin-embedded tissue of Merkel cell carcinoma and correlation with prognosis.
abstract: Merkel cell carcinoma (MCC) is a rare, but highly aggressive primary cutaneous malignancy, showing neuroendocrine differentiation. In 2008, a novel member of the polyomavirus family, named Merkel cell polyomavirus (MCPyV) was identified in the genome of MCC tumors raising the possibility of an involvement in its pathogenesis. Due to the rarity of this tumor and current pathology practices, the most readily available tissue is archival formalin-fixed, paraffin-embedded (FFPE) material. In this study, we evaluated the presence of MCPyV in FFPE tissue and correlated its presence with tumor progression. Representative FFPE specimens from 18 tumors belonging to 14 patients with a diagnosis of MCC spanning the period from 2003 to 2008 were retrieved. Following DNA extraction, we performed PCR amplification and sequencing with four different MCPyV-specific primer pairs mapping within the T antigen and VP1 region. Overall, we detected MCPyV amplicons in 8/18 (44.4%) analyzed tumors from 7/14 (50%) cases. Two-year survival rate and median survival for the MCPyV-positive MCCs were 48% and 22.5 months, respectively and for the negative ones 69% and 51.3 months, respectively; however, the difference did not reach statistical significance (p=0.8). There was no significant correlation between the presence of the virus and the stage at presentation; however, tumors in the head and neck area had a lower frequency of viral positivity compared to those arising in the extremities suggesting a MCPyV-independent oncogenetic pathway perhaps, dependent on UV exposure, in a subset of these cases.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA; andeaa@med.umich.edu.
authors.forename: Aleodor A
authors.initials: AA
authors.lastname: Andea
authors.forename: Raj
authors.initials: R
authors.lastname: Patel
authors.forename: Selvarangan
authors.initials: S
authors.lastname: Ponnazhagan
authors.forename: Tatyana
authors.initials: T
authors.lastname: Isayeva
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.forename: Gene P
authors.initials: GP
authors.lastname: Siegal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000473:pathology* / Q000821:virology*; D004587:Electrophoresis, Agar Gel; D005260:Female; D005557:Formaldehyde / Q000737:chemistry*; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D059965:Merkel cell polyomavirus / Q000302:isolation & purification*; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D016707:Tissue Fixation
chemical_list: D005557:Formaldehyde