Journal of the National Cancer Institute Advance Access originally published online on June 17, 2009
JNCI Journal of the National Cancer Institute 2009 101(13):938-945; doi:10.1093/jnci/djp139
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma
Affiliations of authors: Laboratory of Molecular Oncology, Biomedicum, Helsinki, Finland (HS, HJ); Department of Plastic Surgery (HK, VK) and Department of Oncology (HJ), Helsinki University Central Hospital, Helsinki, Finland; Finnish Cancer Registry, Helsinki, Finland (RS); Department of Pathology, HUSLAB, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland (TB)
Correspondence to: Heikki Joensuu, MD, Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 8, PO Box 180, FIN-00029 Helsinki, Finland (e-mail: heikki.joensuu{at}hus.fi).
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.
| CONTEXT AND CAVEATS Prior knowledge Merkel cell carcinoma is a rare malignancy of the skin in which Merkel cell polyomavirus (MCPyV) DNA is frequently found to be integrated into the tumor genome. Study design Histopathologic and molecular biological analyses of tumor tissue and DNA from Finnish patients who were diagnosed with Merkel cell carcinoma. Contribution MCPyV DNA–positive Merkel cell cancers tended to be located in a limb, have less frequent nodal metastases at the time of the diagnosis, and were associated with better Merkel cell carcinoma–specific and overall survival compared with MCPyV DNA–negative cancers. Implications MCPyV may have a role in the molecular pathogenesis of many Merkel cell carcinomas. Limitations Approximately 45% of the identified Merkel cell carcinoma patients were excluded from the analysis for various reasons, which might have resulted in selection bias. From the Editors
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Manuscript received November 5, 2008; revised April 14, 2009; accepted April 21, 2009.
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J Natl Cancer Inst 2009 101: 901.
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J. A. DeCaprio Does Detection of Merkel Cell Polyomavirus in Merkel Cell Carcinoma Provide Prognostic Information? J Natl Cancer Inst, July 1, 2009; 101(13): 905 - 907. [Full Text] [PDF]
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