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
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).
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.
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.
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
