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. 2015 Jun 15;5(7):2330-43.
eCollection 2015.

Immunohistochemical, genetic and epigenetic profiles of hereditary and triple negative breast cancers. Relevance in personalized medicine

Rosa Murria  1 , Sarai Palanca  1 , Inmaculada de Juan  1 , Cristina Alenda  2 , Cecilia Egoavil  2 , Francisco J Seguí  2 , Zaida García-Casado  3 , María J Juan  4 , Ana B Sánchez  5 , Ángel Segura  6 , Ana Santaballa  7 , Isabel Chirivella  8 , Marta Llop  1 , Gema Pérez  1 , Eva Barragán  1 , Dolores Salas  9 , Pascual Bolufer  1
Affiliations

Immunohistochemical, genetic and epigenetic profiles of hereditary and triple negative breast cancers. Relevance in personalized medicine

Rosa Murria et al. Am J Cancer Res. .

Abstract

This study aims to identify the profile of immunohistochemical (IHC) parameters, copy number aberrations (CNAs) and epigenetic alterations [promoter methylation (PM) and miR expression] related to hereditary (H) and triple negative (TN) breast cancer (BC). This profile could be of relevance for guiding tumor response to treatment with targeting therapy. The study comprises 278 formalin fixed paraffin-embedded BCs divided into two groups: H group, including 88 hereditary BC (HBC) and 190 non hereditary (NHBC), and TN group, containing 79 TNBC and 187 non TNBC (NTNBC). We assessed IHC parameters (Ki67, ER, PR, HER2, CK5/6, CK18 and Cadherin-E), CNA of 20 BC related genes, and PM of 24 tumor suppressor genes employing MLPA/MS-MLPA (MRC Holland, Amsterdam). MiR-4417, miR-423-3p, miR-590-5p and miR-187-3p expression was assessed by quantitative RT-PCR (Applied Biosystems). Binary logistic regression was applied to select the parameters that better differentiate the HBC or TN groups. For HBC we found that, ER expression, ERBB2 CNA and PM in RASSF1 and TIMP3 were associated with NHBC whereas; MYC and AURKA CNA were linked to HBC. For TNBC, we found that CDC6 CNA, GSTP1 and RASSF1 PM and miR-423-3p hyperexpression were characteristic of NTNBC, while MYC aberrations, BRCA1 hypermethylation and miR-590-5p and miR-4417 hyperexpression were more indicative of TNBC. The selected markers allow establishing BC subtypes, which are characterized by showing similar etiopathogenetic mechanisms, some of them being molecular targets for known drugs or possible molecular targets. These results could be the basis to implement a personalized therapy.

Keywords: BRCA1; BRCA2; Sporadic breast cancer; hereditary breast cancer; miR expression profile; molecular markers; mutations.

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Figures

Figure 1
Figure 1
Immunohistochemical, CNA, PM and miR expression profiles for the best differentiation of HBC and NHBC. Binary stepwise backward Wald logistic regression. IHC: immunohistochemical markers; CNA: Copy number aberration; PM: Promoter methylation; NHBC: No hereditary breast cancer; HBC: Hereditary breast cancer.
Figure 2
Figure 2
Immunohistochemical, CNA, PM and miR expression profiles for the best differentiation of TNBC and NTNBC. Binary stepwise backward Wald logistic regression. IHC: immunohistochemical markers; CNA: Copy number aberration; PM: Promoter methylation; NTNBC: No Triple negative breast cancer; TNBC: Triple negative breast cancer.
Figure 3
Figure 3
Immunohistochemical and molecular profiles for the best differentiation of the HBC/NHBC (A) and TNBC/NTNBC phenotypes (B). Binary stepwise backward Wald logistic regression.
See this image and copyright information in PMC

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