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Open Access 01-12-2015 | Research

Evaluation of the prognostic significance of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) validation study

Authors: Angelos Koutras, Konstantine T Kalogeras, Ralph M Wirtz, Zoi Alexopoulou, Mattheos Bobos, Flora Zagouri, Elke Veltrup, Eleni Timotheadou, Helen Gogas, George Pentheroudakis, Nikolaos Pisanidis, Christina Magkou, Christos Christodoulou, Dimitrios Bafaloukos, Pavlos Papakostas, Gerasimos Aravantinos, Dimitrios Pectasides, Haralambos P Kalofonos, George Fountzilas

Published in: Journal of Translational Medicine | Issue 1/2015

Abstract

Background

The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as a validation analysis of another previously published HeCOG study.

Methods

RNA was extracted from 663 formalin-fixed paraffin-embedded (FFPE) tumor tissue samples of high-risk early breast cancer patients enrolled in the randomized HE10/00 trial. Relative mRNA expression of all four HER family members was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results

In compliance with our previous study, the overall agreement between qRT-PCR and IHC/FISH for HER2 status determination was good (69%). Likewise, the overall concordance between qRT-PCR and IHC for EGFR status was high (81%). In line with our previously reported data, we demonstrated a positive association between HER2 and HER3 mRNA expression. Similarly, mRNA expression of HER3 and HER4 was positively associated with each other and negatively associated with EGFR. Regarding relationships with clinico-pathological parameters, our findings are also in agreement with our previous results. Generally, increased EGFR and HER2 mRNA expression was related to unfavorable, whereas high HER3 and HER4 mRNA expression was associated with favorable clinico-pathological parameters. In univariate analysis, no significant association between EGFR, HER2 and HER3 mRNA expression and overall survival (OS) or disease-free survival (DFS) was demonstrated. However, high EGFR protein expression was associated with significantly shorter OS (log-rank, p = 0.015). In compliance with our previously published data, increased HER4 mRNA expression had a significantly favorable prognostic value in terms of OS (p = 0.044) and DFS (p = 0.047). In multivariate analysis, among all HER receptors, only EGFR protein expression was found to affect OS (Wald’s p = 0.028) and DFS (p = 0.015) independently. Concerning the combined expression of all four HER family receptors, the combination of high EGFR, high HER2, low HER3 and low HER4 mRNA expression was associated with a trend for shorter OS (log-rank, p = 0.065) and significantly worse DFS (p = 0.033), compared with all other co-expression profiles.

Conclusions

These data indicate that qRT-PCR may represent a valid alternative method for evaluating the expression of HER family members in FFPE breast carcinoma tissue samples.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12609001036202

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Title: Evaluation of the prognostic significance of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) validation study
Authors: Angelos Koutras
Konstantine T Kalogeras
Ralph M Wirtz
Zoi Alexopoulou
Mattheos Bobos
Flora Zagouri
Elke Veltrup
Eleni Timotheadou
Helen Gogas
George Pentheroudakis
Nikolaos Pisanidis
Christina Magkou
Christos Christodoulou
Dimitrios Bafaloukos
Pavlos Papakostas
Gerasimos Aravantinos
Dimitrios Pectasides
Haralambos P Kalofonos
George Fountzilas
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-015-0530-0

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Abstract

Background

Methods

Results

Conclusions

Trial registration

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