EGFR Overexpression and Sequence Analysis of KRAS, BRAF, and EGFR Mutation Hot Spots in Canine Intestinal Adenocarcinoma

Vet Pathol. 2021 Jul;58(4):674-682. doi: 10.1177/03009858211009778. Epub 2021 Apr 30.

Abstract

Epidermal growth factor receptor (EGFR) is overexpressed in many human colorectal cancers and anti-EGFR agents are employed as immunotherapies. However, KRAS, EGFR, and BRAF gene mutations can influence the activity of the anti-EGFR agents. We evaluated EGFR expression at protein and mRNA levels in canine intestinal adenocarcinomas using immunohistochemistry (IHC) and RNA in situ hybridization (RNA-ISH). We also investigated the mutation status of EGFR, KRAS, and BRAF to aid the development of anti-EGFR agents for canine intestinal adenocarcinoma. EGFR expression was highest in adenocarcinoma, followed by intramucosal neoplasia (adenoma and in situ carcinoma), and nonneoplastic canine intestinal tissue, at both protein (P = .000) and mRNA (P = .005) levels. The EGFR, KRAS, and BRAF genes showed wild-type sequences at the mutation hot spots in all 13 specimens. Thus, EGFR might serve as a promising diagnostic marker in canine intestinal adenocarcinoma, and further studies would be needed to develop EGFR-targeted anticancer therapies.

Keywords: BRAF; EGFR; KRAS; canine intestinal adenocarcinoma; mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / veterinary
  • Animals
  • Dog Diseases*
  • Dogs
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Mutation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Sequence Analysis / veterinary
  • ras Proteins / genetics

Substances

  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins