Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype

Vilma Yuzbasiyan-Gurkan,Matti Kiupel,David A Wiese,Tuddow Thaiwong

doi:10.1186/1471-2407-13-403

Vilma Yuzbasiyan-Gurkan, Matti Kiupel + Show 2 more

Open Access

https://doi.org/10.1186/1471-2407-13-403

Copy DOI

Abstract

BackgroundBreast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC.MethodsTwenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs.ResultsIHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis.ConclusionFMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required to elucidate a potential role of BRCA in the tumorigenesis of triple negative, basal-like FMAs. The strong similarities in clinical behavior, morphology and IHC phenotype suggest that triple negative, basal-like FMAs may be a suitable spontaneous animal model for studying novel therapeutic approaches against human basal-like TNBC.

Highlights

Breast cancer is one of the leading causes of cancer deaths
Histological grading On histopathologic review (Table 1), 3 of the 24 Feline mammary adenocarcinomas (FMAs) were fairly pure papillary carcinomas with well-defined papillary structures identified through a majority of the tumors
FMAs are typically aggressive with a significant propensity to metastasize and usually exhibit morphological features similar to human breast cancer; as such, they have been proposed as a model for human breast cancers [15,16]

Summary

Introduction

Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. While basal-like breast cancer has the worst clinical outcome measured in time to development of distant metastasis [8], there is still some controversy on the histologic classification of this subtype regarding whether triple negative status is required for making the diagnosis of basal-like carcinoma. TNBC have a high incidence in younger, premenopausal patients with higher prevalence in African-American women, and are associated with germ-line BRCA1 mutations [11]

Objectives

Methods

Results

Discussion

Conclusion