Introduction: Epidermal growth factor receptor (EGFR or HER-1) and its homologue c-erbB-2 (HER-2) are tyrosine kinase receptors related to prognosis and response to therapy that are overexpressed in several human and animal cancers. KRAS mediates the transduction of signals between EGFR and the nucleus and KRAS mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology the importance of the HER-1-2/KRAS signalling pathway in gastric cancer is established, and accurate HER testing is considered necessary. This pathway has never been investigated in canine gastric tumours. Materials and Methods: A total of 16 canine gastric tumors (four adenomas and 12 carcinomas) were studied retrospectively by immunohistochemistry (EGFR and HER-2) and nine cases (two adenomas and seven carcinomas) underwent direct sequencing for KRAS analysis. Results: EGFR was mildly expressed (1+) in two carcinomas and overexpressed in 50% of adenomas. HER-2 was overexpressed (2+, 3+) in all cases; KRAS was always wild type in expression. Conclusions: HER-2 is overexpressed in canine gastric tumours. In contrast, EGFR overexpression is mostly limited to adenomas. EGFR/HER-2 expression in gastric adenomas suggests their possible progression to carcinomas. Testing and therapeutic targeting of HER-2 may be promising in canine gastric cancer and advocates for considering the dog as a suitable model for human gastric cancer.

ASSESSMENT OF EGFR AND HER-2 EXPRESSION AND ERAS-STATUS IN CANINE GASTRIC TUMOURS

BETTINI, GIULIANO;MORINI, MARIA;SABATTINI, SILVIA;
2013

Abstract

Introduction: Epidermal growth factor receptor (EGFR or HER-1) and its homologue c-erbB-2 (HER-2) are tyrosine kinase receptors related to prognosis and response to therapy that are overexpressed in several human and animal cancers. KRAS mediates the transduction of signals between EGFR and the nucleus and KRAS mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology the importance of the HER-1-2/KRAS signalling pathway in gastric cancer is established, and accurate HER testing is considered necessary. This pathway has never been investigated in canine gastric tumours. Materials and Methods: A total of 16 canine gastric tumors (four adenomas and 12 carcinomas) were studied retrospectively by immunohistochemistry (EGFR and HER-2) and nine cases (two adenomas and seven carcinomas) underwent direct sequencing for KRAS analysis. Results: EGFR was mildly expressed (1+) in two carcinomas and overexpressed in 50% of adenomas. HER-2 was overexpressed (2+, 3+) in all cases; KRAS was always wild type in expression. Conclusions: HER-2 is overexpressed in canine gastric tumours. In contrast, EGFR overexpression is mostly limited to adenomas. EGFR/HER-2 expression in gastric adenomas suggests their possible progression to carcinomas. Testing and therapeutic targeting of HER-2 may be promising in canine gastric cancer and advocates for considering the dog as a suitable model for human gastric cancer.
Bettini G; A Casadei Gardini; R Terragni; L Capelli; M Morini; S Sabattini; M Vignoli; JH Saunders; P Ulivi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/214507
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