Volume 119, Issue 12 pp. 2974-2979
Short Report

Identification and meta-analysis of a small gene expression signature for the diagnosis of estrogen receptor status in invasive ductal breast cancer

Jörg Schneider

Jörg Schneider

Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg 69120, Germany

The first two authors contributed equally to this paper.

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Markus Ruschhaupt

Markus Ruschhaupt

Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg 69120, Germany

IBE, Medical School, LMU München, München 81377, Germany

The first two authors contributed equally to this paper.

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Andreas Buneß

Andreas Buneß

Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg 69120, Germany

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Martin Asslaber

Martin Asslaber

Institute of Pathology, Medical University of Graz, Graz 8036, Austria

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Peter Regitnig

Peter Regitnig

Institute of Pathology, Medical University of Graz, Graz 8036, Austria

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Kurt Zatloukal

Kurt Zatloukal

Institute of Pathology, Medical University of Graz, Graz 8036, Austria

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Walter Schippinger

Walter Schippinger

Institute of Clinical Oncology, Medical University of Graz, Graz 8036, Austria

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Ferdinand Ploner

Ferdinand Ploner

Institute of Clinical Oncology, Medical University of Graz, Graz 8036, Austria

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Annemarie Poustka

Annemarie Poustka

Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg 69120, Germany

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Holger Sültmann

Corresponding Author

Holger Sültmann

Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg 69120, Germany

Fax: ++49-6221-423454

Im Neuenheimer Feld 580, 69120 Heidelberg, GermanySearch for more papers by this author
First published: 26 October 2006
Citations: 32

The experiments were performed in accordance with the Austrian ethical requirements and were approved by the ethics commission at the University of Graz (No. 12-159 ex 01/02).

Abstract

In breast cancer, the determination of estrogen receptor (ER) expression is crucial for the decision on therapeutic strategies. Current ER expression analysis is based on immunohistochemical (IHC) staining of ER on formalin fixed tissue sections. However, low levels of ER expression frequently escape detection because of varying sensitivities of routine histopathological laboratories. Moreover, in estimating ER by IHC the receptor protein only is tested instead of the complex underlying ER pathway, which reflects its biological activity. To overcome this limitation, we have used the microarray technology to study 56 samples of invasive ductal carcinoma. We infer a robust and reliable signature of 10 genes, which is associated with ER expression and presumably therapeutically relevant biological processes. In a meta-analysis, the signature was tested on 3 further independent microarray gene expression data sets, covering different laboratories, array platforms, and clinics. The classification based on the signature showed a very low misclassification rate. In summary, the expression of few genes is sufficient to determine ER status. Future decisions on antiestrogen based therapy in breast cancer could be based on this signature rather than on immunostaining alone. © 2006 Wiley-Liss, Inc.

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