Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
J Vet Med Sci. 2023 Nov 18;85(11):1195-1209. doi: 10.1292/jvms.23-0322. Epub 2023 Sep 22.
Merkel cell carcinoma (MCC) is a rare skin tumor that shares a similar immunophenotype with Merkel cells, although its origin is debatable. More than 80% of human MCC cases are associated with Merkel cell polyomavirus infections and viral gene integration. Recent studies have shown that the clinical and pathological characteristics of feline MCC are comparable to those of human MCC, including its occurrence in aged individuals, aggressive behavior, histopathological findings, and the expression of Merkel cell markers. More than 90% of feline MCC are positive for the Felis catus papillomavirus type 2 (FcaPV2) gene. Molecular changes involved in papillomavirus-associated tumorigenesis, such as increased p16 and decreased retinoblastoma (Rb) and p53 protein levels, were observed in FcaPV2-positive MCC, but not in FcaPV2-negative MCC cases. These features were also confirmed in FcaPV2-positive and -negative MCC cell lines. The expression of papillomavirus E6 and E7 genes, responsible for p53 degradation and Rb inhibition, respectively, was detected in tumor cells by in situ hybridization. Whole genome sequencing revealed the integration of FcaPV2 DNA into the host feline genome. MCC cases often develop concurrent skin lesions, such as viral plaque and squamous cell carcinoma, which are also associated with papillomavirus infection. These findings suggest that FcaPV2 infection and integration of viral genes are involved in the development of MCC in cats. This review provides an overview of the comparative pathology of feline and human MCC caused by different viruses and discusses their cell of origin.
默克尔细胞癌 (Merkel cell carcinoma, MCC) 是一种罕见的皮肤肿瘤，与默克尔细胞具有相似的免疫表型，尽管其起源存在争议。超过 80%的人类 MCC 病例与 Merkel 细胞多瘤病毒感染和病毒基因整合有关。最近的研究表明，猫的 MCC 的临床和病理特征与人类 MCC 相似，包括在老年个体中发生、侵袭性行为、组织病理学发现和 Merkel 细胞标志物的表达。超过 90%的猫 MCC 对猫细小病毒 2 型 (Felis catus papillomavirus type 2, FcaPV2) 基因呈阳性。在 FcaPV2 阳性的 MCC 中观察到与乳头瘤病毒相关的肿瘤发生相关的分子变化，如 p16 增加和视网膜母细胞瘤 (retinoblastoma, Rb) 和 p53 蛋白水平降低，但在 FcaPV2 阴性的 MCC 病例中没有观察到。这些特征在 FcaPV2 阳性和阴性的 MCC 细胞系中也得到了证实。通过原位杂交在肿瘤细胞中检测到负责 p53 降解和 Rb 抑制的乳头瘤病毒 E6 和 E7 基因的表达。全基因组测序显示 FcaPV2 DNA 整合到宿主猫的基因组中。MCC 病例常伴有皮肤病变，如病毒性斑块和鳞状细胞癌，这些病变也与乳头瘤病毒感染有关。这些发现表明 FcaPV2 感染和病毒基因的整合参与了猫的 MCC 的发生。本综述概述了不同病毒引起的猫和人 MCC 的比较病理学，并讨论了它们的起源细胞。
