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

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.

Keywords: RNA in situ hybridization; c-KIT; canine cutaneous mast cell tumour; immunohistochemistry; mRNA.

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Dog Diseases / metabolism*
  • Dog Diseases / pathology
  • Dogs
  • Female
  • Gene Expression Regulation, Neoplastic
  • Male
  • Mastocytoma / metabolism
  • Mastocytoma / pathology
  • Mastocytoma / veterinary*
  • Prognosis
  • Proto-Oncogene Proteins c-kit / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Skin Neoplasms / veterinary*

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Proto-Oncogene Proteins c-kit