Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?

Canine mammary tumors (CMTs) share many features
with human breast cancer (HBC), specifically
concerning cancer-related pathways. Although the human epidermal
growth factor receptor 2 (HER2) plays a significant
role as a therapeutic and prognostic biomarker in HBC, its
relevance in the pathogenesis and prognosis of CMT is still
controversial. The aim of this study was to investigate HER2
expression in canine mammary hyperplasic and neoplastic
tissues as well as to evaluate the specificity of the most commonly
used polyclonal anti HER2 antibody by multiple molecular
approaches. HER2 protein and RNA expression were
determined by immunohistochemistry (IHC) and by quantitative
real-time (qRT) PCR. A strong cell membrane associated
with non-specific cytoplasmic staining was observed in 22 %
of carcinomas by IHC. Adenomas and carcinomas exhibited a
significantly higher HER2 mRNA expression when compared
to normal mammary glands, although no significant difference
between benign and malignant tumors was noticed by qRTPCR.
The IHC results suggest a lack of specificity of the
FDA-approved antibody in CMT samples as further
demonstrated by Western immunoblotting (WB) and reverse
phase protein arrays (RPPA). Furthemore, HER2 was not detected
by mass spectrometry (MS) in a protein-expressing
carcinoma at the IHC investigation. This study highlights that
caution needs to be used when trying to translate from human
to veterinary medicine information concerning cancer-related
biomarkers and pathways. Further investigations are necessary
to carefully assess the diagnostic and biological role specifically
exerted by HER2 in CMTs and the use of canine
mammary tumors as a model of HER2 over-expressing breast
cancer.