Rac proteins of the Rho-like
GTPase family, including the ubiquitous Rac1, the hematopoiesis-specific Rac2, and the least-characterized Rac3 play a major role in oncogenic transformation,
tumor invasion and
metastasis. However, the prognostic relevance of Rac expression in human
tumors has not been investigated yet. In the present study, Rac
protein expression was analyzed in benign secretory epithelium, high-grade prostatic intraepithelium
neoplasia (HG-PIN), and prostate
carcinomas of 60 R0-resected radical
prostatectomy specimens by semiquantitative immunohistochemistry. Thus,
Rac proteins were significantly strongly expressed in HG-PIN (P < 0.001) and prostate
carcinomas (P < 0.001) when compared with benign secretory epithelium. Accordingly, all
tumor tissues analyzed by
isoform-specific real-time PCR (n = 7) exhibited significantly higher
RNA expression levels of Rac (i.e. sum of Rac1 and Rac3 expression levels) than the respective benign counterparts (P = 0.018) and this appeared to result mainly from increased expression of the Rac3
isoform as verified by immunoblotting. Univariate analyses showed statistically significant associations of increased Rac
protein expression in
prostate cancer (P = 0.045), preoperative
prostate-specific antigen levels (P = 0.044), pT stage (P = 0.002), and Gleason score (P = 0.001) with decreased disease-free survival (DFS). This prognostic effect of increased
protein expression of Rac remained significant even in a multivariate analysis including all these four factors (relative risk = 3.22, 95% confidence interval = 1.04-10.00; P = 0.043). In conclusion, our data suggest that increased Rac
protein expression in
prostate cancer relative to the corresponding benign secretory epithelium is an independent predictor of decreased DFS and appears to result mainly from increased expression of the Rac3
isoform.