Year-end Sale % OFF 
Abstract
IntroductionTypical 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).MethodsExpression 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.ResultsAll 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.ConclusionOur 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.
Highlights
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 Medullary breast carcinomas (MBCs)
Basal-like carcinomas (BLCs) were characterized by a specific immunophenotype that was negative for estrogen receptor (ER), progesterone receptor (PR) and ERBB2, and positive for cytokeratin (KRT) type 5/6, KRT 14 or KRT 17, epidermal growth factor receptor (EGFR) and KIT; [5,6] they were associated with TP53 mutations [3]
Clinical characteristics of patients Because several studies have shown a higher incidence of MBCs in young patients, in particular in a BRCA1 context, we compared the ages of the two groups of patients (MBC group: median 53.5 years; range 34 to 76 years; basal-like carcinomas (BLC) group: median 60 years; range 37 to 82 years; Table 1)
Summary
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. Medullary breast carcinomas (MBCs) represent 2% of all invasive breast carcinomas, and these tumors show aggressive pathological features they are often associated with a more favorable outcome. They are defined by an association of five morphological features [1]: a predominantly syncytial growth pattern, a circumscribed border, a moderate to marked lymphoplasmacytic infiltrate, poorly differentiated nuclear grade with high mitotic rate, and the absence of glandular features or any in situ component. We and others have demonstrated that MBCs have a favorable outcome despite the aggressive pathological features at presentation [11,12,13] and unlike basal-like tumors [5]. These analyses reveal that MBCs have distinct specificities, both at the immunophenotypic level, including more frequent cytokeratin 5/6 expression, and at the genomic level with a high level of chromosome gains and losses, recurrent 10p, 9p and 16q gains and 4p losses, and 1q, 8q, 10p and 12p amplicons
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
