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PLoS One. 2014 Jan 15;9(1):e85388. doi: 10.1371/journal.pone.0085388. eCollection 2014.

EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

Author information

1
Veterinary Oncology Center, Sasso Marconi, Italy ; Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
2
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
3
Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
4
Petcare Veterinary Association, Marzabotto, Italy.
5
Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.

Abstract

Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥ 1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

PMID:
24454858
PMCID:
PMC3893207
DOI:
10.1371/journal.pone.0085388
[Indexed for MEDLINE]
Free PMC Article

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