Research article

Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer

Jocelyne Jacquemier^1,2 , Emmanuelle Charafe-Jauffret^1,2,3 , Florence Monville¹ , Benjamin Esterni⁴ , Jean Marc Extra⁵ , Gilles Houvenaeghel⁶ , Luc Xerri^2,3 , François Bertucci^1,3,5 and Daniel Birnbaum¹

¹  Département d'Oncologie Moléculaire Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, UMR891 Inserm; IFR137, 232 Bd sainte Marguerite Marseille, 13009 France

²  Département de BioPathologie, Institut Paoli-Calmettes, 232 Bd sainte Marguerite Marseille,13009 France

³  UFR de Médecine, Université de la Méditerranée, 58 Bd Charles Livon Marseille 13284, France

⁴  Département de Biostatistiques, Institut Paoli-Calmettes, 232 Bd Ste Marguerite Marseille 13009, France

⁵  Département d'Oncologie Médicale, Institut Paoli-Calmettes, 232 Bd Ste Marguerite Marseille 13009, France

⁶  Département d'Oncologie Chirurgicale, Institut Paoli-Calmettes, 232 Bd Ste Marguerite Marseille 13009, France

author email corresponding author email

Breast Cancer Research 2009, 11:R23doi:10.1186/bcr2249

Published:	30 April 2009

Abstract

Introduction

Breast cancers are traditionally divided into hormone-receptor positive and negative cases. This classification helps to guide patient management. However, a subgroup of hormone-receptor positive patients relapse irrespective of hormonal therapy. Gene expression profiling has classified breast tumours into five major subtypes with significant different outcome. The two luminal subtypes, A and B, show high expression of ESR1, GATA3 and FOXA1 genes. Prognostic biomarkers for oestrogen receptor (ER)-positive cases include progesterone receptor (PR) and androgen receptor (AR), and proteins related to proliferation or apoptotic resistance. The aim of this study was to identify the best predictors of success of hormonal therapy.

Methods

By immunohistochemistry we studied 10 markers in a consecutive series of 832 cases of breast carcinoma treated at the Paoli-Calmettes Institute from 1990 to 2002 and deposited onto tissue microarrays (TMA). These markers were luminal-related markers ER, PR, AR, FOXA1 and GATA3 transcription factors, proliferation-related Ki67 and CCND1, ERBB2, anti-apoptotic BCL2 and P53. We also measured vascular peritumoural invasion (VPI), size, grade and lymph node involvement. For 143 cases, gene expression profiles were available. Adjuvant chemotherapy and hormonal therapy were given to high- and low-risk patients, respectively. The 162 events observed and taken into account were metastases.

Results

Molecular expression of the 10 parameters and subtype with ER status were strongly correlated. Of the 67 luminal A cases of this series, 63 were ER-positive. Multivariate analyses showed the highly significant prognostic value of VPI (hazard ratio (HR) = 2.47), Ki67 (HR = 2.9), P53 (HR = 2.9) and GATA3 (HR = 0.5) for the 240 patients who received hormonal therapy.

Conclusions

A panel of three antibodies (Ki67, P53 and GATA3) associated with VPI can significantly improve the traditional prognosticators in predicting outcome for ER-positive breast cancer patients receiving hormonal therapy.