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Breast Cancer Research
Published in: Breast Cancer Research 2/2009

Open Access 01-04-2009 | Research article

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

Authors: Achim Rody, Uwe Holtrich, Laos Pusztai, Cornelia Liedtke, Regine Gaetje, Eugen Ruckhaeberle, Christine Solbach, Lars Hanker, Andre Ahr, Dirk Metzler, Knut Engels, Thomas Karn, Manfred Kaufmann

Published in: Breast Cancer Research | Issue 2/2009

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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.
Appendix
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Metadata
Title
T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers
Authors
Achim Rody
Uwe Holtrich
Laos Pusztai
Cornelia Liedtke
Regine Gaetje
Eugen Ruckhaeberle
Christine Solbach
Lars Hanker
Andre Ahr
Dirk Metzler
Knut Engels
Thomas Karn
Manfred Kaufmann
Publication date
01-04-2009
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2009
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2234

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