Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity.
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.
Vincent-Salomon
Anne
A
Department of Tumor Biology, Institut Curie, Paris cedex 05, France. anne.salomon@curie.net
Gruel
Nadège
N
Lucchesi
Carlo
C
MacGrogan
Gaëtan
G
Dendale
Remi
R
Sigal-Zafrani
Brigitte
B
Longy
Michel
M
Raynal
Virginie
V
Pierron
Gaëlle
G
de Mascarel
Isabelle
I
Taris
Corinne
C
Stoppa-Lyonnet
Dominique
D
Pierga
Jean-Yves
JY
Salmon
Rémy
R
Sastre-Garau
Xavier
X
Fourquet
Alain
A
Delattre
Olivier
O
de Cremoux
Patricia
P
Aurias
Alain
A
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
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53