Data from Merkel Cell Polyomavirus Infection, Large T Antigen, Retinoblastoma Protein and Outcome in Merkel Cell Carcinoma

Abstract

<div>Abstract<p><b>Purpose:</b> Merkel cell carcinoma (MCC) is rare skin cancer that is often associated with Merkel cell polyomavirus (MCPyV) infection. Polyomaviruses repress tumor suppressor proteins, thus influencing cell-cycle progression, but the effect of MCPyV on the key cell-cycle regulating proteins is poorly understood.</p><p><b>Experimental Design:</b> We evaluated expression of the MCPyV large T-antigen (LTA), Ki-67, and the key putative tumor suppressor proteins, the retinoblastoma protein (RB and phospho-RB) and p53, and their regulatory proteins (cyclin D1, cyclin E, p16, p21, p27, and MDM2) by using immunohistochemistry from tumors of 91 MCC patients identified from a population-based nationwide cohort. Tumor MCPyV DNA was measured by using quantitative PCR, and <i>TP53</i> mutations were identified with sequencing.</p><p><b>Results:</b> MCPyV LTA expression was strongly associated with presence of MCPyV DNA in tumor, and it was almost invariably associated with tumor RB expression (<i>P</i> < 0.0001 for both comparisons). Both MCC LTA and RB expression were strongly associated with favorable MCC-specific and overall survival in univariable analyses (<i>P</i> ≤ 0.01 for all four analyses). Presence of MCPyV LTA was also associated with the female gender, the intermediate type of tumor histology, location of the tumor in a limb, cell proliferation rate, and absence of p53 expression. <i>TP53</i> mutations were detected only in MCPyV DNA–negative tumors.</p><p><b>Conclusions:</b> MCPyV DNA–positive MCC has several clinical and molecular features that differ from MCPyV DNA-negative cancers. MCPyV-associated MCCs express RB, but may not harbor <i>TP53</i> mutations. These findings provide further support that MCPyV causes the majority of MCCs. <i>Clin Cancer Res; 17(14); 4806–13. ©2011 AACR</i>.</p></div>