title: Prognostic relevance of Tiam1 protein expression in prostate carcinomas.
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. > or =3.5-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. > or =7) (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.
authors.affiliation: Institute of Pathology, Heinrich-Heine-University, Moorenstrasse 5, Duesseldorf D-40225, Germany. engers@med.uni-duesseldorf.de
authors.forename: R
authors.initials: R
authors.lastname: Engers
authors.forename: M
authors.initials: M
authors.lastname: Mueller
authors.forename: A
authors.initials: A
authors.lastname: Walter
authors.forename: J G
authors.initials: JG
authors.lastname: Collard
authors.forename: R
authors.initials: R
authors.lastname: Willers
authors.forename: H E
authors.initials: HE
authors.lastname: Gabbert
mesh_terms: D000368:Aged; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human