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01.01.2013 | Original Article

Prognostic significance of RACGAP1 mRNA expression in high-risk early breast cancer: a study in primary tumors of breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial

verfasst von: K. Pliarchopoulou, K. T. Kalogeras, R. Kronenwett, R. M. Wirtz, A. G. Eleftheraki, A. Batistatou, M. Bobos, N. Soupos, G. Polychronidou, H. Gogas, E. Samantas, C. Christodoulou, T. Makatsoris, N. Pavlidis, D. Pectasides, G. Fountzilas

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2013

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Abstract

Purpose

RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI).

Methods

A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression.

Results

High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS (p < 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald’s p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (p = 0.016), while high NPI score values were not.

Conclusions

High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts.

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Titel: Prognostic significance of RACGAP1 mRNA expression in high-risk early breast cancer: a study in primary tumors of breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial
verfasst von: K. Pliarchopoulou
K. T. Kalogeras
R. Kronenwett
R. M. Wirtz
A. G. Eleftheraki
A. Batistatou
M. Bobos
N. Soupos
G. Polychronidou
H. Gogas
E. Samantas
C. Christodoulou
T. Makatsoris
N. Pavlidis
D. Pectasides
G. Fountzilas
Publikationsdatum: 01.01.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-2002-z

Springer Medizin

Prognostic significance of RACGAP1 mRNA expression in high-risk early breast cancer: a study in primary tumors of breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial