Premium
The molecular underpinning of lobular histological growth pattern: a genome‐wide transcriptomic analysis of invasive lobular carcinomas and grade‐ and molecular subtype‐matched invasive ductal carcinomas of no special type
Author(s) -
Weigelt Britta,
Geyer Felipe C,
Natrajan Rachael,
LopezGarcia Maria A,
Ahmad Amar S,
Savage Kay,
Kreike Bas,
ReisFilho Jorge S
Publication year - 2010
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2629
Subject(s) - biology , transcriptome , gene expression profiling , phenotype , cancer research , apocrine , gene , epigenetics , periostin , gene signature , pathology , gene expression , microbiology and biotechnology , genetics , medicine , extracellular matrix , anatomy
Invasive lobular carcinoma (ILC) is the most frequent special type of breast cancer. The majority of these tumours are of low histological grade, express hormone receptors, and lack HER2 expression. The pleomorphic variant of ILCs (PLCs) is characterized by atypical cells with pleomorphic nuclei and is reported to have an aggressive clinical behaviour. Expression profiling studies have demonstrated that classic ILCs preferentially display a luminal phenotype, whereas PLCs may be of luminal, HER2 or molecular apocrine subtypes. The aims of this study were two‐fold: to determine the transcriptomic characteristics of lobular carcinomas and to define the genome‐wide transcriptomic differences between classic ILCs and PLCs. To define the transcriptomic characteristics of ILCs, minimizing the impact of histological grade and molecular subtype on the analysis, we subjected a series of grade‐ and molecular subtype‐matched ILCs and invasive ductal carcinomas (IDCs) to genome‐wide gene expression profiling using oligonucleotide microarrays. Hierarchical clustering analysis demonstrated that ILCs formed a separate cluster and a supervised analysis revealed that 5.8% of the transcriptionally regulated genes were significantly differentially expressed in ILCs compared to grade‐ and molecular subtype‐matched IDCs. ILCs displayed down‐regulation of E‐cadherin and of genes related to actin cytoskeleton remodelling, protein ubiquitin, DNA repair, cell adhesion, TGF‐beta signalling; and up‐regulation of transcription factors/immediate early genes, lipid/prostaglandin biosynthesis genes, and cell migration‐associated genes. Supervised analysis of classic ILCs and PLCs demonstrated that less than 0.1% of genes were significantly differentially expressed between these tumour subtypes. Our results demonstrate that ILCs differ from grade‐ and molecular subtype‐matched IDCs in the expression of genes related to cell adhesion, cell‐to‐cell signalling, and actin cytoskeleton signalling. However, classic ILCs and PLCs are remarkably similar at the molecular level and should be considered as part of a spectrum of lesions. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.