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Recently, a new human polyoma virus has been identified in Merkel cell carcinomas (MCC). MCC is a highly aggressive neuroendocrine nonmelanoma skin cancer (NMSC) associated with immunosuppression. Clonal integration of this virus which was termed Merkel cell polyoma virus (MCPyV) was reported in a number of MCC. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are also NMSC and are the most frequent cancers in the setting of immunosuppression. A unique group of 56 NMSC from 11 immunosuppressed patients and 147 NMSC of 125 immunocompetent patients was tested for MCPyV by DNA PCR, targeting the Large T Antigen and the structural Viral Protein 1. NMSC included SCC, BCC and Bowen's disease (BD). In addition, normal skin and 89 colorectal cancers were tested. MCPyV specific sequences were significantly more frequently found in NMSC of immunosuppressed patients compared to immunocompetent patients (p < 0.001). In particular BD and BCC revealed a significant increased association of MCPyV of immunosuppressed patients (p 5 0.002 and p 5 0.006). Forty-seven of 147 (32%) sporadic NMSC were MCPyV positive. Interestingly, 37.5% (36/96) of sporadic BCC of immunocompetent patients were MCPyV positive. No MCPyV was detected within normal skin and only 3 out of 89 of additionally tested colorectal cancers were MCPyV positive. Our data show that MCPyV is a frequently reactivated virus in immunocompromized patients. How MCPyV contributes to the pathogenesis of NMSC, i.e., BD, SCC and BCC, in immunosuppressed patients and in addition, potentially to the pathogenesis of a subset of sporadic BCC needs further investigations. ' UICCKey words: nonmelanoma skin cancer (NMSC); merkel cell polyoma virus (MCPyV); immunosuppression Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are nonmelanoma skin cancers (NMSC) and in this order constitute the most frequent cancers associated with immunosuppression in transplant recipients. [1][2][3][4][5][6] According to the steadily increasing number of transplant operations performed each year in the European Union and the United States, post-transplant skin cancer is a leading medical issue in current transplantation medicine. To date a number of risk factors for the increasing number of NMSC under immunosuppression have been identified. 2 In addition to SCC and BCC, other NMSC, i.e., sebaceous cancers, cutaneous lymphomas and Merkel cell carcinomas (MCC) occur more frequently in post-transplant patients. 7,8 MCC has been described relatively recently and is a rare but very aggressive malignant neuroendocrine skin cancer of the elderly and immunosuppressed. [8][9][10] Very recently, Feng et al. reported the identification of a new human polyoma virus which was designated Merkel cell polyomavirus (MCPyV) based on its detection in MCC by digital transcriptome subtraction technique. 11 They reported the presence of MCPyV in 8 of 10 human MCC and also clonal integration of the viral DNA in 6 of 8 MCPyV-positive MCC. Analyzing the first large number patient cohort of MCC by PCR...

Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine nonmelanoma skin cancer, which is associated with the Merkel cell polyoma virus (MCPyV). Recently, expression of the terminal deoxynucleotidyl transferase (TdT) and the paired box gene 5 (PAX 5) has been consistently reported in the majority of

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