Abstract 3772A: Merkel cell polyomavirus infection in Merkel cell carincoma

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Abstract OBJECTIVE: The newly discovered Merkel cell polyomavirus (MCV) may play a role in the etiology of Merkel cell carcinoma (MCC), a rare neuroendocrine malignancy of the skin, as several studies have demonstrated MCV DNA in tumor tissues. However, MCV serologic data are sparse, with few studies investigating MCV DNA in tumor tissues and MCV antibodies within the same patients, and no published data on antibodies to MCV T-antigen. We conducted a pilot study to evaluate MCV antibody profiles in MCC cases versus controls and to examine the correlation between MCV DNA in tumors and MCV seroreactivity. METHODS: Plasma samples were obtained from 33 patients diagnosed and/or treated for MCC at the Moffitt Cancer Center in 2006-08, including 25 males and 8 females, ages 53-88 years. Controls were comprised of 37 patients undergoing routine skin cancer screening exams who had no history of skin cancer and were determined to be negative for all types of non-melanoma skin cancer (NMSC) by a nurse practitioner. Fresh-frozen tumor tissue was obtained from 15 MCC patients, including 9 from whom plasma was also obtained. Virus-like particle-based enzyme linked immunosorbent assays (ELISA) were used to measure IgG and IgA antibodies to the MCV VP1 capsid protein. Levels of IgG directed against MCV large T-antigen were also measured using ELISA. MCV DNA was measured in MCC tumor tissues using real-time polymerase chain reaction for the amplification of the small T-antigen region of the MCV genome. Differences in antibody levels across groups were assessed using Wilcoxon rank sum test. RESULTS: Levels of IgG directed against the MCV capsid protein were higher among MCC cases than healthy controls (mean (SD)= 1876 (4001) in cases, 1521 (4889) in controls; p=0.005), as were levels of MCV capsid IgA (mean (SD) = 0.21 (0.25) and 0.09 (0.15) p=0.005). Although levels of IgG antibodies directed against the large T-antigen were slightly higher among MCC cases compared to healthy controls (mean (SD) =0.25 (0.27) vs. 0.19(0.07)), this difference was not statistically significant. MCV DNA was observed in 10 (67%) of 15 tumor tissues tested, with viral loads ranging from 7.1 to 15.6 viral copies per cell equivalent. Levels of IgG antibodies directed against MCV capsid and T-antigen were higher among the 6 MCV DNA-positive cases than the 3 MCV DNA-negative cases for whom plasma was available (mean (SD): capsid IgG: 1040 (1210) in MCV DNA-positive, 384 (494) in MCV DNA-negative, p=0.52; T-antigen IgG: 0.26 (0.26) in MCV DNA-positive, 0.15 (0.15) in MCV DNA-negative, p=0.52). CONCLUSION: MCV seroreactivity is associated with MCC, and MCV antibody levels are higher among MCC patients with MCV DNA-positive tumor tissues. A larger study is needed to confirm these associations with greater statistical power and provide the evidence needed to establish causality between MCV infection and MCC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3772A.