EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?
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.
Veterinary Oncology Center, Sasso Marconi, Italy ; Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
Rossella
R
Terragni
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Andrea
A
Casadei Gardini
Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Silvia
S
Sabattini
Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Giuliano
G
Bettini
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Dino
D
Amadori
Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Chiara
C
Talamonti
Petcare Veterinary Association, Marzabotto, Italy.
Massimo
M
Vignoli
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Laura
L
Capelli
Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
Jimmy H
JH
Saunders
Marianna
M
Ricci
Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
Marianna
M
Ricci
Paola
P
Ulivi
Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
Paola
P
Ulivi
D000293:Adolescent; D000818:Animals; D001483:Base Sequence; D002648:Child; D017931:DNA Primers; D004195:Disease Models, Animal; D004285:Dogs; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D066246:ErbB Receptors