Journal of the National Cancer Institute Advance Access originally published online on September 23, 2009
JNCI Journal of the National Cancer Institute 2009 101(21):1510-1522; doi:10.1093/jnci/djp332
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ARTICLES |
Association of Merkel Cell Polyomavirus–Specific Antibodies With Merkel Cell Carcinoma
Affiliations of authors: Program in Cancer Biology (JJC, GCW, DM, DAG), Division of Human Biology (JJC, MMM, LGJ, DAG), Division of Public Health Sciences (JJC, MMM, LGJ, DAG), and Division of Clinical Research (PN), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Microbiology (DAG), Department of Pathology (KGP, SL, PN), Department of Epidemiology (MMM), Department of Dermatology/Medicine (KGP, BDL, SL, AHW, JGI, PN), University of Washington, Seattle, WA
Correspondence to: Denise A. Galloway, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M.S. C1-105, Seattle, WA 98109-1024 (e-mail: dgallowa{at}fhcrc.org).
Background: Merkel cell polyomavirus (MCPyV) has been detected in approximately 75% of patients with the rare skin cancer Merkel cell carcinoma. We investigated the prevalence of antibodies against MCPyV in the general population and the association between these antibodies and Merkel cell carcinoma.
Methods: Multiplex antibody-binding assays were used to assess levels of antibodies against polyomaviruses in plasma. MCPyV VP1 antibody levels were determined in plasma from 41 patients with Merkel cell carcinoma and 76 matched control subjects. MCPyV DNA was detected in tumor tissue specimens by quantitative polymerase chain reaction. Seroprevalence of polyomavirus-specific antibodies was determined in 451 control subjects. MCPyV strain–specific antibody recognition was investigated by replacing coding sequences from MCPyV strain 350 with those from MCPyV strain w162.
Results: We found that 36 (88%) of 41 patients with Merkel cell carcinoma carried antibodies against VP1 from MCPyV w162 compared with 40 (53%) of the 76 control subjects (odds ratio adjusted for age and sex = 6.6, 95% confidence interval [CI] = 2.3 to 18.8). MCPyV DNA was detectable in 24 (77%) of the 31 Merkel cell carcinoma tumors available, with 22 (92%) of these 24 patients also carrying antibodies against MCPyV. Among 451 control subjects from the general population, prevalence of antibodies against human polyomaviruses was 92% (95% CI = 89% to 94%) for BK virus, 45% (95% CI = 40% to 50%) for JC virus, 98% (95% CI = 96% to 99%) for WU polyomavirus, 90% (95% CI = 87% to 93%) for KI polyomavirus, and 59% (95% CI = 55% to 64%) for MCPyV. Few case patients had reactivity against MCPyV strain 350; however, indistinguishable reactivities were found with VP1 from strain 350 carrying a double mutation (residues 288 and 316) and VP1 from strain w162.
Conclusion: Infection with MCPyV is common in the general population. MCPyV, but not other human polyomaviruses, appears to be associated with Merkel cell carcinoma.
| CONTEXT AND CAVEATS Prior knowledge Approximately 75% of patients with the rare skin cancer Merkel cell carcinoma appear to carry Merkel cell polyomavirus (MCPyV). Study design A retrospective case–control study was used to study levels of antibodies against polyomaviruses in plasma from 41 patients with Merkel cell carcinoma and 76 matched control subjects. Seroprevalence of polyomavirus-specific antibodies was determined in another 451 control subjects, who represented the general population. MCPyV DNA was detected in tumor tissue specimens. Contribution The authors found that 36 (88%) patients with Merkel cell carcinoma carried antibodies against MCPyV compared with 40 (53%) control subjects. MCPyV DNA was detectable in 24 (77%) of the 31 Merkel cell carcinoma tumors available, with 22 (92%) of these patients also carrying antibodies against MCPyV. Among 451 control subjects from the general population, prevalence of antibodies against the five human polyomaviruses was 92% for BK virus, 45% for JC virus, 98% for WU polyomavirus, 90% for KI polyomavirus, and 59% for MCPyV. Implications Although infection with MCPyV is common in the general population, MCPyV, but not the other four human polyomaviruses, appears to be associated with Merkel cell carcinoma. Limitations The case–control study was small. Study subjects were primarily white, so that results may not be generalizable. There is no "gold standard" for determining MCPyV positive or negative status. From the Editors
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Manuscript received January 30, 2009; revised July 27, 2009; accepted August 25, 2009.
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