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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Fernando Schmitt (Autor) FMUP

Revista

Título: Journal of Pathology

Vol. 215

Páginas: 231-244

ISSN: 0022-3417

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 116 Citações

Scopus - 135 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

CORDIS: Ciências da Saúde > Ciências Médicas > Medicina > Anatomia patológica

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14