Merkel Cell Polyomavirus Infection, Large T Antigen, Retinoblastoma Protein and Outcome in Merkel Cell Carcinoma
Merkel Cell Polyomavirus Infection, Large T Antigen, Retinoblastoma Protein and Outcome in Merkel Cell Carcinoma
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DOI：
10.1158/1078-0432.ccr-10-3363
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发表时间：
2011-07-15
影响因子：
11.5
通讯作者：
Joensuu, Heikki
中科院分区：
文献类型：
--
作者：
Sihto, Harri;Kukko, Heli;Joensuu, Heikki
Purpose: 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.Experimental Design: 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 TP53 mutations were identified with sequencing.Results: MCPyV LTA expression was strongly associated with presence of MCPyV DNA in tumor, and it was almost invariably associated with tumor RB expression (P < 0.0001 for both comparisons). Both MCC LTA and RB expression were strongly associated with favorable MCC-specific and overall survival in univariable analyses (P
