Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer

Takayuki Iwamoto, Giampaolo Bianchini, Yuan Qi, Massimo Cristofanilli, Anthony Lucci, Wendy A. Woodward, James M. Reuben, Junji Matsuoka, Yun Gong, Savitri Krishnamurthy, Vicente Valero, Gabriel N. Hortobagyi, Fredika Robertson, W. Fraser Symmans, Lajos Pusztai*, Naoto T. Ueno

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The goal of this study was to determine whether gene expression differences exist between inflammatory breast cancers (IBC) and T stage-matched non-IBC patients stratified by hormone receptor and HER2 status. We used Affymetrix GeneChips to analyze 82 tumor samples (25 T4d patients, and 57 T4a-c patients) of newly diagnosed breast cancers. Genes that were differentially expressed between the IBC and non-IBC specimens were identified using the t test, and differential expression of gene sets was assessed using gene set analysis. Three distinct clinical subtypes of IBC and non-IBC were compared: ER-positive/HER2-normal, HER2-amplified, and ER-negative/HER2-normal. When we compared expression data from all IBC with all non-IBC, we found no significant differences after adjusting for multiple testing. When IBC and non-IBC tumors were compared by clinical subtype, however, significant differences emerged. Complement and immune system-related pathways were overexpressed in ER-positive/HER2-normal IBC. Protein translation and mTOR signaling were overexpressed in HER2-amplified IBC. Apoptosis-, neural-, and lipid metabolism-related pathways were overexpressed in ER-negative/HER2-normal IBC compared with non-IBC of the same receptor phenotype. In this T stage-matched case-control study, the survival curves of patients with IBC and non-IBC were similar for all three clinical subtypes. IBC tumors can be divided into molecular and clinical subtypes similar to those of non-IBC. Clinical subtypes of IBC show molecular differences compared with similar subtypes of non-IBC.

Original languageEnglish (US)
Pages (from-to)785-795
Number of pages11
JournalBreast Cancer Research and Treatment
Volume125
Issue number3
DOIs
StatePublished - Feb 2011

Keywords

  • Gene set analysis
  • Inflammatory breast cancer
  • Receptor subtypes
  • cDNA microarray

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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