HER-2 expression in canine morphologically normal, hyperplastic and neoplastic mammary tissues and its correlation with the clinical outcome

Abstract

The proto-oncogene HER-2/neu (c-erbB-2) encodes a transmembrane receptor protein with tyrosine-kinase activity. Previous studies have shown that HER-2 protein over-expression is present in canine mammary tumours, however, possible prognostic and predictive analogies between protein over-expression patterns in canine and human species are still controversial. Thirty-five canine mammary carcinomas, 11 mammary adenomas, and normal, hyperplastic or dysplastic tissues taken at the marginal area of the tumours were evaluated by immunohistochemistry (IHC) for HER-2 expression, using the Hercept Test® system scoring guidelines. HER-2 over-expression was detected in 3/11 adenomas and 10/35 carcinomas. Normal, hyperplastic and dysplastic mammary tissues were also found to be positive. The correlations between HER-2 expression and tumour histological grading, mitotic index, the presence of lymphatic invasion, and overall survival (OS) were evaluated. In carcinomas, HER-2 positive status only correlated with the mitotic index. A positive correlation was also found between HER-2 positive status and the presence of HER-2 over-expression in normal, hyperplastic or/and dysplastic mammary tissues surrounding the tumours. The percentage of HER-2 over-expressing tumours was similar to the percentage previously observed in canine benign and malignant mammary tumours. However an investigation regarding morphologically normal and hyperplastic or dysplastic tissues surrounding neoplastic lesions also showed HER-2 over-expression. In contrast with human mammary tumours, this study confirmed that in canine species, HER-2 over-expression does not identify a subgroup of tumours with a poor prognosis. In fact, we found HER-2 over-expression in morphologically non-neoplastic mammary tissues, surrounding hyperplastic and neoplastic lesions.