Molecular profiling pleomorphic lobular carcinomas of the breast: evidence for a common molecular genetic pathway with classic lobular carcinomas

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Fernando Schmitt (Author) FMUP

Journal

Title: Journal of Pathology

Vol. 215

Pages: 231-244

ISSN: 0022-3417

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 120 Citations

Scopus - 143 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences > Medical sciences > Medicine > Pathological anatomy

Other information

Authenticus ID: P-003-Y70

DOI: 10.1002/path.2358

Abstract (EN): Pleomorphic lobular carcinomas (PLC) of the breast display histological features associated with classic invasive lobular carcinoma (ILC), yet they also exhibit more conspicuous nuclear atypia and pleomorphism, and an aggressive clinical behaviour. From a breast cancer progression perspective, it is unclear whether PLC is a variant of ILC or is a high-grade invasive ductal carcinoma (IDC) that has lost E-cadherin. The molecular features of 26 PLC were studied using immunohistochemistry [oestrogen receptor (ER), progesterone receptor (PR), HER2, p53 and E-cadherin], 0.9 Mb resolution, microarray-based comparative genomic hybridization (aCGH), fluorescent (FISH) and chromogenic (CISH) in situ hybridization and loss of heterozygosity. Comparative analysis was performed with aCGH data from PLC with classic ILC (16 cases) and high grade IDC (35 cases). PLCs were frequently ER- and PR-positive, E-cadherin-negative and occasionally HER2-and p53-positive. Recurrent copy number changes identified by aCGH included gains on 1q, 8q, 11q, 12q, 16p and 17q and losses on 8p, 11q, 13q, 16q and Xq. Highly recurrent 1q+ (100% of cases), 16p+ (93%), 11q- (53%) and 16q- (93%) and evidence of the der(1;16)/der(16)t(1;16) rearrangement, as detected by FISH, suggested that PLC had a 'lobular genotype'. Focal amplifications were evident at 8p12-p11, 8q24, 11q13.1-q14.1, 12q14,17q12 and 20q13. Loss of BRCA2 was detected in 40% of PLC by LOH. Comparative analysis of aCGH data suggested the molecular features of PLC (ER/PR-positive, E-cad herin-negative, 1q(+), 11q(-), 16p(+) and 16q(-)) were more closely related to those of ILC than IDC, implicating an overlapping developmental pathway for these lobular tumour types. Molecular alterations found in PLC that are more typical of high-grade IDC than ILC (p53 and HER2 positivity, 8q(+), 17q24-q25(+), 13q(-) and amplification of 8q24, 12q14, 17q12 and 20q13) are likely to drive the high-grade and more aggressive biology of PLC. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14