Department of Veterinary Pathology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
Vet Comp Oncol. 2021 Mar;19(1):132-139. doi: 10.1111/vco.12650. Epub 2020 Nov 3.
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.
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。