Abstract
Abstract Merkel cell polyomavirus (MCV) is a recently discovered human oncogenic virus. The majority of Merkel cell carcinomas (MCC) have been found to be infected with MCV. The MCV large T antigen (LTA) consists of an Rb binding motif that is functionally analogous to the E7 protein of high-risk human papillomavirus (HPV) types (eg. 16 and 18). It has been well documented that inactivation of Rb leads to overexpression of p16INK4a. Clinically, immunohistochemistry for p16INK4a has proven useful in the diagnosis of HPV driven epithelial malignancies including cervical as well as head and neck cancers. The present study explores the relationship between MCV infection and p16INK4a expression using an in vitro cell culture system and 10 clinical specimens of MCC that have been diagnosed at the San Diego VA Hospital over a 21 year period. First, IMR-90 cells were transfected with MCV LTA plasmids, which carry either wild-type or mutant Rb binding motif for immunofluorescence analysis. Only cells transfected with wild-type, but not mutant LTA, were associated with p16INK4a up-regulation. Furthermore, a strong positive correlation was established between MCV LTA and p16INK4a expression in formalin-fixed, paraffin-embedded MCC samples by immunohistochemical staining using p16INK4a and MCV LTA specific monoclonal antibodies, and real-time PCR to detect MCV with two pairs of primers. In conclusion, strong association between p16INK4a expression and MCC suggests that the MCV and HPV related carcinomas share some common oncogenic pathways. In addition, p16INK4a positivity can be a useful diagnostic tool in differentiating MCC from other small blue cell tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2716. doi:10.1158/1538-7445.AM2011-2716
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