Molecular Diagnostics

British Journal of Cancer (2006) 95, 1081–1086. doi:10.1038/sj.bjc.6603385 www.bjcancer.com
Published online 26 September 2006

Prognostic relevance of Tiam1 protein expression in prostate carcinomas

R Engers1, M Mueller2, A Walter1, J G Collard3, R Willers4 and H E Gabbert1

  1. 1Institute of Pathology, Heinrich-Heine-University, Moorenstrasse 5, Duesseldorf D-40225, Germany
  2. 2Department of Urology, Heinrich-Heine-University, Moorenstrasse 5, Duesseldorf D-40225, Germany
  3. 3The Netherlands Cancer Institute, Department of Cell Biology, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands
  4. 4Department of Computational Statistics, Heinrich-Heine-University, Moorenstrasse 5, Duesseldorf D-40225, Germany

Correspondence: PD Dr R Engers, E-mail: engers@med.uni-duesseldorf.de

Received 30 June 2006; Revised 29 August 2006; Accepted 31 August 2006; Published online 26 September 2006.

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Abstract

The Rac-specific guanine nucleotide exchange factor, Tiam1, plays a major role in oncogenicity, tumour invasion and metastasis but its usefulness as a prognostic marker in human cancer has not been tested yet. In the present study, Tiam1 expression was analysed in benign secretory epithelium, pre-neoplastic high-grade prostatic intraepithelium neoplasia (HG-PIN) and prostate carcinomas of 60 R0-resected radical prostatectomy specimens by semiquantitative immunohistochemistry. Tiam1 proved significantly overexpressed in both HG-PIN (P<0.001) and prostate carcinomas (P<0.001) when compared to benign secretory epithelium. Strong Tiam1 overexpression (i.e. greater than or equal to3.5-fold) in prostate carcinomas relative to the respective benign prostatic epithelium was statistically significantly associated with disease recurrence (P=0.016), the presence of lymph vessel invasion (P=0.031) and high Gleason scores (GS) (i.e. greater than or equal to7) (P=0.044). Univariate analysis showed a statistically significant association of strong Tiam1 overexpression with decreased disease-free survival (DFS) (P=0.03). This prognostic effect of strong Tiam1 overexpression remained significant in multivariate analysis including preoperative prostate-specific antigen levels, pT stage, and GS (relative risk= 3.75, 95% confidence interval=1.06–13.16; P=0.04). Together, our data suggest that strong Tiam1 overexpression relative to the corresponding benign epithelial cells is a new and independent predictor of decreased DFS for patients with prostate cancer.

Keywords:

Tiam1, Rac, prognosis, prostate cancer, proliferation