Open Access Highly Accessed Research article

Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15

Jacqueline Lehmann-Che123, Anne-Sophie Hamy4*, Raphaël Porcher5, Marc Barritault12, Fatiha Bouhidel6, Hanadi Habuellelah4, Solenne Leman-Detours4, Anne de Roquancourt6, Laurence Cahen-Doidy8, Edwige Bourstyn4, Patricia de Cremoux123, Cedric de Bazelaire9, Marcela Albiter9, Sylvie Giacchetti4, Caroline Cuvier4, Anne Janin67, Marc Espié4, Hugues de Thé123 and Philippe Bertheau367*

Author Affiliations

1 AP-HP, Hosp Saint-Louis, Laboratory of Biochemistry, 1 av C. Vellefaux, Paris, 75010, France

2 CNRS UMR7212/INSERMU944, IUH, 1 av C. Vellefaux, Paris, 75010, France

3 University Paris Diderot, Sorbonne Paris Cité, Paris, 75010, France

4 AP-HP, Hosp Saint-Louis, Breast Diseases Center, 1 av C. Vellefaux, Paris, 75010, France

5 AP-HP, Hosp Saint-Louis, Biostatistic Department, 1 av C. Vellefaux, Paris 75010, France

6 AP-HP, Hosp Saint-Louis, Laboratory of Pathology, 1 av C. Vellefaux, Paris, 75010, France

7 INSERM UMR_S728, 1 av C. Vellefaux, Paris, 75010, France

8 AP-HP, Hosp Saint-Louis, Department of Surgery, 1 av C. Vellefaux, Paris, 75010, France

9 AP-HP, Hosp Saint-Louis, Department of Radiology, 1 av C. Vellefaux, Paris, 75010, France

For all author emails, please log on.

Breast Cancer Research 2013, 15:R37  doi:10.1186/bcr3421

Published: 11 May 2013

Abstract

Introduction

Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors.

Methods

We performed quantitative reverse transcription PCR (qRT-PCR) for ESR1, AR, FOXA1 and AR-related genes, and immunohistochemistry (IHC) for ER, PR, Human Epidermal Growth Factor Receptor 2 (HER2), CK5/6, CK17, EGFR, Ki67, AR, FOXA1 and GCDFP15 and we analyzed clinical features.

Results

MA tumors were all characterized by ESR1(-) AR(+) FOXA1(+) and AR-related genes positive mRNA profile. IHC staining on these tumors showed 93% ER(-), only 58% AR(+) and 90% FOXA1(+). 67% and 57% MA tumors were HER2(3+) and GCDFP15(+), respectively. Almost all MA tumors (94%) had the IHC signature HER2(3+) or GCDFP15(+) but none of the 13 control basal-like (BL) tumors did. Clinically, MA tumors were rather aggressive, with poor prognostic factors.

Conclusion

MA tumors could be better defined by their qRT-PCR-AR profile than by AR IHC. In addition, we found that HER2 or GCDFP15 protein overexpression is a sensitive and specific tool to differentiate MA from BL in the context of ER negative tumors. A composite molecular and IHC signature could, therefore, help to identify MA tumors in daily practice.

Keywords:
cancer; breast carcinoma; molecular apocrine; estrogen receptor; HER2; GCDFP15; triple negative; basal-like