title: Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Tumor Biology, Institut Curie, Paris cedex 05, France. anne.salomon@curie.net
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Nadège
authors.initials: N
authors.lastname: Gruel
authors.forename: Carlo
authors.initials: C
authors.lastname: Lucchesi
authors.forename: Gaëtan
authors.initials: G
authors.lastname: MacGrogan
authors.forename: Remi
authors.initials: R
authors.lastname: Dendale
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
authors.forename: Virginie
authors.initials: V
authors.lastname: Raynal
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.forename: Isabelle
authors.initials: I
authors.lastname: de Mascarel
authors.forename: Corinne
authors.initials: C
authors.lastname: Taris
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.forename: Rémy
authors.initials: R
authors.lastname: Salmon
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Patricia
authors.initials: P
authors.lastname: de Cremoux
authors.forename: Alain
authors.initials: A
authors.lastname: Aurias
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D016000:Cluster Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018295:Neoplasms, Basal Cell / Q000145:classification* / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53