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犬皮肤肥大细胞瘤原位 c-KIT mRNA 定量及其与预后因素的关系。

In situ c-KIT mRNA quantification of canine cutaneous mast cell tumours and its relationship to prognostic factors.

机构信息

Department of Veterinary Pathology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.

出版信息

Vet Comp Oncol. 2021 Mar;19(1):132-139. doi: 10.1111/vco.12650. Epub 2020 Nov 3.

Abstract

Cutaneous mast cell tumours (MCTs) are the most frequent malignant skin tumours in dogs. Mutations in the c-KIT proto-oncogene are correlated with the pathogenesis and aggressiveness of MCTs. To date, studies have focused on c-KIT mutations and KIT protein localization, with a general lack of mRNA-level analyses. In this study, c-KIT mRNA expression was investigated in canine MCTs by RNA in situ hybridization (RNA-ISH). Furthermore, we evaluated associations between c-KIT mRNA expression and the histological grade, KIT immunohistochemical staining pattern and other clinicopathological parameters. c-KIT mRNA expression was observed in all MCT samples, appearing as clusters of dots in the cytoplasm of neoplastic cells. A significant correlation was detected between c-KIT mRNA expression (quantified according to the H-score and the percentage of positive cells) and the histological grade (determined using two-and three-tier grading systems; P < .05). We also found a significant positive correlation (all P < .05) between c-KIT mRNA expression and the proliferation indices (mitotic index, Ki-67, and Ag67). However, no significant associations with c-KIT expression from RNA-ISH were found with respect to different KIT staining patterns. Overall, these results demonstrate that c-KIT mRNA expression might be an additional tool for measuring the c-KIT status in canine cutaneous MCTs and could serve as a potential prognostic factor. Further studies should evaluate the prognostic significance of c-KIT mRNA expression in a large and uniform cohort of canine MCTs.

摘要

皮肤肥大细胞瘤(MCT)是犬最常见的恶性皮肤肿瘤。c-KIT 原癌基因突变与 MCT 的发病机制和侵袭性相关。迄今为止,研究主要集中在 c-KIT 突变和 KIT 蛋白定位上,普遍缺乏 mRNA 水平分析。在本研究中,通过 RNA 原位杂交(RNA-ISH)研究了犬 MCT 中的 c-KIT mRNA 表达。此外,我们评估了 c-KIT mRNA 表达与组织学分级、KIT 免疫组织化学染色模式和其他临床病理参数之间的相关性。在所有 MCT 样本中均观察到 c-KIT mRNA 表达,表现为肿瘤细胞细胞质中的点状簇。根据 H 评分和阳性细胞百分比对 c-KIT mRNA 表达进行定量分析,发现其与组织学分级(使用二分层和三分层分级系统确定;P <.05)之间存在显著相关性。我们还发现 c-KIT mRNA 表达与增殖指数(有丝分裂指数、Ki-67 和 Ag67)之间存在显著正相关(均 P <.05)。然而,c-KIT mRNA 表达与 RNA-ISH 不同的 KIT 染色模式之间没有显著相关性。总之,这些结果表明,c-KIT mRNA 表达可能是衡量犬皮肤 MCT 中 c-KIT 状态的附加工具,并且可以作为潜在的预后因素。应进一步研究在犬 MCT 的大型和统一队列中评估 c-KIT mRNA 表达的预后意义。

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