Molecular portrait-based correlation between primary canine mammary tumor and its lymph node metastasis: possible prognostic-predictive models and/or stronghold for specific treatments?

Germana Beha,Francesca Millanta,Pietro Asproni,Alessandro Poli,Giuseppe Sarli,Cinzia Benazzi,Barbara Brunetti,Luisa Vera Muscatello

doi:10.1186/1746-6148-8-219

Germana Beha, Francesca Millanta + Show 6 more

Open Access

https://doi.org/10.1186/1746-6148-8-219

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Abstract

BackgroundThis study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options.ResultsTwenty mammary tumor samples and their lymph node metastases were selected and stained by immunohistochemistry with anti-estrogen receptor (ER), -progesterone receptor (PR), -human epidermal growth factor receptor 2 (c-erbB-2), -cytokeratin 5/6 (CK 5/6), -cytokeratin 14 (CK14), -cytokeratin 19 (CK 19) and -protein 63 (p63) antibodies. Four phenotypes (luminal A, luminal B, c-erbB2 overexpressing and basal-like) were diagnosed in primary tumors and five (luminal A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like) in the lymph node metastases. Phenotypic concordance was found in 13 of the 20 cases (65%), and seven cases (35%) showed discordance with different lymph node phenotypic profile from the primary tumor.ConclusionsThe phenotype of the primary tumor assumes a predictive-therapeutic role only in concordant cases, meaning that both the primary tumor and its lymph node metastasis should be evaluated at the same time. A treatment plan based only on the primary tumor phenotype could lead to therapeutic failures if the phenotype of the lymph node metastasis differs from that of the primary tumor.

Highlights

This study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options
Canine mammary tumors and human breast cancer are heterogeneous diseases commonly occurring in female dogs [1,2] and in women [3,4]
Eight of the 20 primary tumors were classified as simple tubulopapillary carcinomas, eight as solid carcinomas, two as complex carcinomas and two as anaplastic carcinomas

Summary

Introduction

This study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options. Canine mammary tumors and human breast cancer are heterogeneous diseases commonly occurring in female dogs [1,2] and in women [3,4]. Sorlie et al [11] examined the human expression profiles of 115 breast carcinomas identifying five subtypes: two hormone (oestrogen and/or progesterone) receptor-positive types (luminal-like A and luminal B) and hormone receptor-negative types [human epidermal growth factor receptor 2- overexpressing, basallike, and unclassified (“normal-like”)]. Based on classification of the human gene expression profile, four main carcinoma subtypes have been identified in canine species [8]: luminal A, luminal B, c-erbB-2 overexpressing and basal-like

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