Research article

T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers

Achim Rody¹ , Uwe Holtrich¹ , Laos Pusztai² , Cornelia Liedtke³ , Regine Gaetje¹ , Eugen Ruckhaeberle¹ , Christine Solbach¹ , Lars Hanker¹ , Andre Ahr¹ , Dirk Metzler⁴ , Knut Engels⁵ , Thomas Karn¹ and Manfred Kaufmann¹

¹  Department of Obstetrics and Gynecology, J.W. Goethe-University, Theodor-Stern-Kai 7, Frankfurt 60590, Germany

²  Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, PO Box 301439, Houston, TX 77230-1439, USA

³  Department of Obstetrics and Gynecology, University of Muenster, Albert-Schweitzer-Straße 33, Muenster 48149, Germany

⁴  LMU BioCenter, Ludwig Maximilians University Munich, Grosshaderner Straße 2, Planegg-Martinsried 82152, Germany

⁵  Department of Pathology, J.W. Goethe-University, Theodor-Stern-Kai 7, Frankfurt 60590, Germany

author email corresponding author email

Breast Cancer Research 2009, 11:R15doi:10.1186/bcr2234

Published:	9 March 2009

Abstract

Introduction

Lymphocyte infiltration (LI) is often seen in breast cancer but its importance remains controversial. A positive correlation of human epidermal growth factor receptor 2 (HER2) amplification and LI has been described, which was associated with a more favorable outcome. However, specific lymphocytes might also promote tumor progression by shifting the cytokine milieu in the tumor.

Methods

Affymetrix HG-U133A microarray data of 1,781 primary breast cancer samples from 12 datasets were included. The correlation of immune system-related metagenes with different immune cells, clinical parameters, and survival was analyzed.

Results

A large cluster of nearly 600 genes with functions in immune cells was consistently obtained in all datasets. Seven robust metagenes from this cluster can act as surrogate markers for the amount of different immune cell types in the breast cancer sample. An IgG metagene as a marker for B cells had no significant prognostic value. In contrast, a strong positive prognostic value for the T-cell surrogate marker (lymphocyte-specific kinase (LCK) metagene) was observed among all estrogen receptor (ER)-negative tumors and those ER-positive tumors with a HER2 overexpression. Moreover ER-negative tumors with high expression of both IgG and LCK metagenes seem to respond better to neoadjuvant chemotherapy.

Conclusions

Precise definitions of the specific subtypes of immune cells in the tumor can be accomplished from microarray data. These surrogate markers define subgroups of tumors with different prognosis. Importantly, all known prognostic gene signatures uniformly assign poor prognosis to all ER-negative tumors. In contrast, the LCK metagene actually separates the ER-negative group into better or worse prognosis.