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Breast Cancer Research
Published in: Breast Cancer Research 3/2007

Open Access 01-06-2007 | Research article

TP53mutation status and gene expression profiles are powerful prognostic markers of breast cancer

Authors: Anita Langerød, Hongjuan Zhao, Ørnulf Borgan, Jahn M Nesland, Ida RK Bukholm, Tone Ikdahl, Rolf Kåresen, Anne-Lise Børresen-Dale, Stefanie S Jeffrey

Published in: Breast Cancer Research | Issue 3/2007

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Abstract

Introduction

Gene expression profiling of breast carcinomas has increased our understanding of the heterogeneous biology of this disease and promises to impact clinical care. The aim of this study was to evaluate the prognostic value of gene expression-based classification along with established prognostic markers and mutation status of the TP53 gene (tumour protein p53) in a group of breast cancer patients with long-term (12 to 16 years) follow-up.

Methods

The clinical and histopathological parameters of 200 breast cancer patients were studied for their effects on clinical outcome using univariate/multivariate Cox regression. The prognostic impact of mutations in the TP53 gene, identified using temporal temperature gradient gel electrophoresis and sequencing, was also evaluated. Eighty of the samples were analyzed for gene expression using 42 K cDNA microarrays and the patients were assigned to five previously defined molecular expression groups. The strength of the gene expression based classification versus standard markers was evaluated by adding this variable to the Cox regression model used to analyze all samples.

Results

Both univariate and multivariate analysis showed that TP53 mutation status, tumor size and lymph node status were the strongest predictors of breast cancer survival for the whole group of patients. Analyses of the patients with gene expression data showed that TP53 mutation status, gene expression based classification, tumor size and lymph node status were significant predictors of survival. Breast cancer cases in the 'basal-like' and 'ERBB2+' gene expression subgroups had a very high mortality the first two years, while the 'highly proliferating luminal' cases developed the disease more slowly, showing highest mortality after 5 to 8 years. The TP53 mutation status showed strong association with the 'basal-like' and 'ERBB2+' subgroups, and tumors with mutation had a characteristic gene expression pattern.

Conclusion

TP53 mutation status and gene-expression based groups are important survival markers of breast cancer, and these molecular markers may provide prognostic information that complements clinical variables. The study adds experience and knowledge to an ongoing characterization and classification of the disease.
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Metadata
Title
TP53mutation status and gene expression profiles are powerful prognostic markers of breast cancer
Authors
Anita Langerød
Hongjuan Zhao
Ørnulf Borgan
Jahn M Nesland
Ida RK Bukholm
Tone Ikdahl
Rolf Kåresen
Anne-Lise Børresen-Dale
Stefanie S Jeffrey
Publication date
01-06-2007
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2007
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1675

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