title: Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma.
abstract: BACKGROUND
  Merkel cell carcinoma is a rare malignancy of the skin. Integration of Merkel cell polyomavirus (MCPyV) DNA to the tumor genome is frequent in these cancers. The clinical consequences of MCPyV infection are unknown.
  
  
  METHODS
  We analyzed formalin-fixed paraffin-embedded Merkel cell carcinoma tissue samples from 114 of 207 patients diagnosed with Merkel cell carcinoma in Finland from 1979 to 2004 for the presence of MCPyV DNA with the use of polymerase chain reaction (PCR), quantitative PCR, and DNA sequencing and examined associations between tumor MCPyV DNA status and histopathologic factors and survival. The median follow-up time after Merkel cell carcinoma diagnosis for subjects who were alive was 9.9 years (range = 4.9-21.9 years). All P values are two-sided.
  
  
  RESULTS
  MCPyV DNA was present in 91 carcinomas (79.8%). Compared with MCPyV DNA-negative cancers, MCPyV DNA-positive cancers were more often located in a limb (40.7% vs 8.7%, P = .015) and less frequent in patients who had regional nodal metastases at diagnosis (6.6% vs 21.7%, P = .043). Patients with MCPyV DNA-positive tumors had better overall survival than those with MCPyV DNA-negative tumors (5-year survival: 45.0% vs 13.0%, respectively; P < .001, two-sided log-rank test).
  
  
  CONCLUSIONS
  MCPyV infection is associated with clinical outcomes in patients with Merkel cell carcinoma. These findings lend support to the hypothesis that viral infection is frequently associated with the pathogenesis of Merkel cell carcinoma.
authors.affiliation: Laboratory of Molecular Oncology, Biomedicum, Helsinki, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Sihto
authors.forename: Heli
authors.initials: H
authors.lastname: Kukko
authors.forename: Virve
authors.initials: V
authors.lastname: Koljonen
authors.forename: Risto
authors.initials: R
authors.lastname: Sankila
authors.forename: Tom
authors.initials: T
authors.lastname: Böhling
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000401:mortality / Q000821:virology*; D004279:DNA, Viral / Q000302:isolation & purification*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D016867:Immunocompromised Host; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000150:complications*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015983:Selection Bias; D012878:Skin Neoplasms / Q000401:mortality / Q000821:virology*
chemical_list: D004279:DNA, Viral