Abstract
Merkel cell polyomavirus (MCPyV) has recently been identified in Merkel cell carcinoma (MCC), an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR) and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9) and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen’s disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]). In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%), BCC (1 case; 2%), and AK (3 cases; 6%). We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119–42.8) and AK (0.02–0.07) groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662). Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4) demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC), but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection.
Highlights
Merkel cell carcinoma (MCC), which is a rare and aggressive primary cutaneous neoplasm that affects elderly and/or immunocompromised individuals, tends to occur in sun-exposed skin [1]
We investigated the frequency of Merkel cell polyomavirus (MCPyV) infection in skin tumors, including MCC and other sun exposurerelated skin tumors, such as basal cell carcinoma (BCC), actinic keratosis (AK), and Bowen’s disease (BD), in Japan
polymerase chain reaction (PCR) Amplification of MCPyV from Skin Tumors We first analyzed whether MCPyV DNA fragments were present or absent in skin tumor tissues by conventional PCR
Summary
Merkel cell carcinoma (MCC), which is a rare and aggressive primary cutaneous neoplasm that affects elderly and/or immunocompromised individuals, tends to occur in sun-exposed skin [1]. The monoclonal integration of MCPyV DNA in host DNA has been demonstrated in neoplastic MCC cells, indicating that the virus causes and/or promotes this specific type of cutaneous neoplasm [2]. It remains unclear how often MCPyV is associated with other cutaneous neoplasms and to what extent racial factors influence the infection rates. In skin tumors other than MCC, MCPyV has been detected at various frequencies (0%–25%) by PCR. MCPyV T-antigen expression may be suppressed in infected cells in certain circumstances, even though MCPyV viral DNA is integrated into the cellular DNA.
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