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Breast Cancer Research
Published in: Breast Cancer Research 2/2007

Open Access 01-12-2007 | Research article

Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity

Authors: Anne Vincent-Salomon, Nadège Gruel, Carlo Lucchesi, Gaëtan MacGrogan, Remi Dendale, Brigitte Sigal-Zafrani, Michel Longy, Virginie Raynal, Gaëlle Pierron, Isabelle de Mascarel, Corinne Taris, Dominique Stoppa-Lyonnet, Jean-Yves Pierga, Rémy Salmon, Xavier Sastre-Garau, Alain Fourquet, Olivier Delattre, Patricia de Cremoux, Alain Aurias

Published in: Breast Cancer Research | Issue 2/2007

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Abstract

Introduction

Typical medullary breast carcinoma (MBC) has recently been recognized to be part of the basal-like carcinoma spectrum, a feature in agreement with the high rate of TP53 mutations previously reported in MBCs. The present study was therefore designed to identify phenotypic and genetic alterations that distinguish MBCs from basal-like carcinomas (BLC).

Methods

Expression levels of estrogen receptor (ER), progesterone receptor (PR), ERBB2, TP53, cytokeratins (KRTs) 5/6, 14, 8/18, epidermal growth factor receptor and KIT, as well as TP53 gene sequence and high-density array comparative genomic hybridization (CGH) profiles, were assessed and compared in a series of 33 MBCs and 26 BLCs.

Results

All tumors were negative for ER, PR and ERBB2. KRTs 5/6 were more frequently expressed in MBCs (94%) than in BLCs (56%) (p = 0.0004). TP53 mutations were disclosed in 20/26 MBCs (77%) and 20/24 BLCs (83%). Array CGH analysis showed that a higher number of gains (95 regions) and losses (34 regions) was observed in MBCs than in BLCs (36 regions of gain; 13 regions of losses). In addition, gains of 1q and 8q, and losses of X were found to be common to the two groups, whereas gains of 10p (53% of the cases), 9p (30.8% of the cases) and 16q (25.8% of the cases), and losses of 4p (34.8% of the cases), and amplicons of 1q, 8p, 10p and 12p were the genetic alterations found to characterize MBC.

Conclusion

Our study has revealed that MBCs are part of the basal-like group and share common genomic alterations with BLCs, the most frequent being 1q and 8q gains and X losses; however, MBCs are a distinct entity within the basal-like spectrum, characterized by a higher rate of KRT 5/6 expression, a higher rate of gains and losses than BLCs, recurrent 10p, 9p and 16q gains, 4p losses, and 1q, 8p, 10p and 12p amplicons. Our results thus contribute to a better understanding of the heterogeneity in basal-like breast tumors and provide potential diagnostic tools.
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Metadata
Title
Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity
Authors
Anne Vincent-Salomon
Nadège Gruel
Carlo Lucchesi
Gaëtan MacGrogan
Remi Dendale
Brigitte Sigal-Zafrani
Michel Longy
Virginie Raynal
Gaëlle Pierron
Isabelle de Mascarel
Corinne Taris
Dominique Stoppa-Lyonnet
Jean-Yves Pierga
Rémy Salmon
Xavier Sastre-Garau
Alain Fourquet
Olivier Delattre
Patricia de Cremoux
Alain Aurias
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2007
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1666

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