Division of Molecular Pathology, Department of Pathology, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
Hum Pathol. 2012 Dec;43(12):2282-91. doi: 10.1016/j.humpath.2012.04.002. Epub 2012 Jul 13.
Merkel cell polyomavirus is a novel polyomavirus that is monoclonally integrated into genomes of up to 80% of human Merkel cell carcinomas. Merkel cell polyomavirus-positive Merkel cell carcinomas showed less metastatic tendency and better prognosis according to some reports, whereas others disagree. In this study, we analyzed clinicopathological characteristics of 20 Merkel cell polyomavirus-positive and 6 Merkel cell polyomavirus-negative Merkel cell carcinoma cases, in which we already reported the association of Merkel cell polyomavirus infection with statistically significant morphological differences. Immunohistochemical expressions of cell cycle-related proteins, mutations of the TP53 tumor-suppressor gene (exons 4-9) and p14ARF promoter methylation status as well as detailed clinical data were analyzed and compared between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative cases. Merkel cell polyomavirus-positive Merkel cell carcinomas showed better prognosis with one spontaneous regression case and significantly higher expression of retinoblastoma protein (P = .0003) and less p53 expression (P = .0005) compared to Merkel cell polyomavirus-negative Merkel cell carcinomas. No significant differences were found in expressions of p63, MDM2, p14ARF or MIB-1 index, and p14ARF promoter methylation status. Interestingly, frequency of TP53 non-ultraviolet signature mutation was significantly higher in Merkel cell polyomavirus-negative Merkel cell carcinomas than in Merkel cell polyomavirus-positive Merkel cell carcinomas (P = .036), whereas no significant difference was detected in TP53 ultraviolet signature mutations between two groups. These results suggest that Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas likely develop through different tumorigenic pathways and that the presence or absence of Merkel cell polyomavirus in the tumor is still an important factor that affects survival in patients with Merkel cell carcinoma.
默克尔细胞多瘤病毒是一种新型的多瘤病毒，它在高达 80%的人类默克尔细胞癌基因组中呈单克隆整合。根据一些报道，默克尔细胞多瘤病毒阳性的默克尔细胞癌转移倾向较小，预后较好，而另一些报道则不同意。在这项研究中，我们分析了 20 例默克尔细胞多瘤病毒阳性和 6 例默克尔细胞多瘤病毒阴性的默克尔细胞癌病例的临床病理特征，我们已经报道了默克尔细胞多瘤病毒感染与统计学上显著的形态学差异有关。在默克尔细胞多瘤病毒阳性和默克尔细胞多瘤病毒阴性病例之间，分析并比较了细胞周期相关蛋白的免疫组织化学表达、TP53 肿瘤抑制基因（外显子 4-9）的突变和 p14ARF 启动子甲基化状态以及详细的临床数据。与默克尔细胞多瘤病毒阴性的默克尔细胞癌相比，默克尔细胞多瘤病毒阳性的默克尔细胞癌预后更好，有 1 例自发消退病例，视网膜母细胞瘤蛋白的表达明显更高（P =.0003），p53 表达明显更低（P =.0005）。p63、MDM2、p14ARF 或 MIB-1 指数的表达和 p14ARF 启动子甲基化状态无显著差异。有趣的是，默克尔细胞多瘤病毒阴性的默克尔细胞癌中 TP53 非紫外线特征性突变的频率明显高于默克尔细胞多瘤病毒阳性的默克尔细胞癌（P =.036），而两组之间 TP53 紫外线特征性突变无显著差异。这些结果表明，默克尔细胞多瘤病毒阳性和阴性的默克尔细胞癌可能通过不同的肿瘤发生途径发展，肿瘤中是否存在默克尔细胞多瘤病毒仍然是影响默克尔细胞癌患者生存的一个重要因素。
