Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status.

Rita Rodrigues,Fátima Cardoso,Andreia Gameiro,Maria Soares,Shabir Najmudin,Fernando Ferreira,Rita Ribeiro

doi:10.18632/oncotarget.7551

Abstract

HER2 is overexpressed in about 30% of feline mammary carcinomas (FMC) and in 15-30% of breast cancers. Women with HER2-positive breast tumors are associated with shorter survival. This study aimed to optimize the detection and quantification of serum HER2 (sHER2) in cats and to evaluate its potential in diagnosing cats with mammary carcinomas (MC) overexpressing HER2. A prospective study was conducted in 60 queens showing MC and 20 healthy animals. Pre-operative serum samples were collected for sHER2 quantification using two immunoassays: ELISA and Dot blot assay. sHER2 levels were compared with tissue HER2 status assessed by immunohistochemistry. Queens with FMC showed significantly higher mean levels of sHER2 by both ELISA and Dot blot assay. A significant difference in the sHER2 levels was also found between cats with HER2-positive MC and those with low-expressing HER2 MC. A significant correlation between sHER2 levels and tumor HER2 status was also found, particularly when ELISA was used (r = 0.58, p < 0.0001). The value of 10 ng/ml was proposed as the optimal cutoff for both immunoassays by ROC analysis. Like in humans, sHER2 levels are increased in cats with MC HER2-positive, strongly suggesting that evaluation of sHER2 levels can be very useful in feline oncology. The results show that ELISA and Dot blot assay can replace the immunohistochemistry technique, due to their efficacy and lower costs for diagnostic purposes and for monitoring the response to anti-HER2 therapies in cats.

Highlights

Animal models have been crucial in increasing our understanding of tumorigenesis, with mouse species being the most commonly used because of their small size and short gestation period [1]
Pre-operative serum samples were collected for serum human epidermal growth factor receptor-2 proto-oncogene (HER2) (sHER2) quantification using two immunoassays: Enzyme-linked immunosorbent assay (ELISA) and Dot blot assay. sHER2 levels were compared with tissue HER2 status assessed by immunohistochemistry
Our results show www.impactjournals.com/oncotarget that sHER2 levels in cats with HER2 overexpressing mammary carcinomas are significantly higher than in cats with HER2-negative mammary carcinomas (p = 0.001) or healthy animals (p = 0.04)

Summary

Introduction

Animal models have been crucial in increasing our understanding of tumorigenesis, with mouse species being the most commonly used because of their small size and short gestation period [1]. Feline mammary carcinomas (FMC) are very common in cats, showing an incidence that ranges from 12 to 40% of all tumors [6, 7]. Their epidemiological and histopathological features closely resemble those found in the more aggressive breast cancer types [8]. It has been proposed as a putative model for cancer studies [2, 8,9,10,11,12,13]. Some reports have shown that the feline homologue of human epidermal growth factor receptor-2 proto-oncogene (HER2) is overexpressed in 33%-60% of FMC [10, 13, 14, 15] and it was associated with a shorter overall survival (OS) [14] as in human HER2 positive breast tumors, even though the HER2 gene amplification could not be detected [10, 13]

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