EGFR, HER-2 and KRAS in canine gastric epithelial tumors

A potential human model?

Rossella Terragni, Andrea Casadei Gardini, Silvia Sabattini, Giuliano Bettini, Dino Amadori, Chiara Talamonti, Massimo Vignoli, Laura Capelli, Jimmy H. Saunders, Marianna Ricci, Paola Ulivi

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 intestinaltype 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.

Original languageEnglish
Article numbere85388
JournalPLoS One
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 15 2014

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Stomach Neoplasms
Canidae
Tumors
Stomach
stomach
stomach neoplasms
Focal Adhesion Kinase 1
neoplasms
Glandular and Epithelial Neoplasms
dogs
carcinoma
Neoplasms
Oncology
therapeutics
Carcinoma
Epidermal Growth Factor Receptor
Mucinous Adenocarcinoma
Pharmaceutical Preparations
Mutation
mutation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

EGFR, HER-2 and KRAS in canine gastric epithelial tumors : A potential human model? / Terragni, Rossella; Gardini, Andrea Casadei; Sabattini, Silvia; Bettini, Giuliano; Amadori, Dino; Talamonti, Chiara; Vignoli, Massimo; Capelli, Laura; Saunders, Jimmy H.; Ricci, Marianna; Ulivi, Paola.

In: PLoS One, Vol. 9, No. 1, e85388, 15.01.2014.

Research output: Contribution to journalArticle

Terragni, R, Gardini, AC, Sabattini, S, Bettini, G, Amadori, D, Talamonti, C, Vignoli, M, Capelli, L, Saunders, JH, Ricci, M & Ulivi, P 2014, 'EGFR, HER-2 and KRAS in canine gastric epithelial tumors: A potential human model?', PLoS One, vol. 9, no. 1, e85388. https://doi.org/10.1371/journal.pone.0085388
Terragni, Rossella ; Gardini, Andrea Casadei ; Sabattini, Silvia ; Bettini, Giuliano ; Amadori, Dino ; Talamonti, Chiara ; Vignoli, Massimo ; Capelli, Laura ; Saunders, Jimmy H. ; Ricci, Marianna ; Ulivi, Paola. / EGFR, HER-2 and KRAS in canine gastric epithelial tumors : A potential human model?. In: PLoS One. 2014 ; Vol. 9, No. 1.
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