1. ¹Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Institut für Pathologie, Neuherberg, Germany
2. ²Technische Universität München, Klinikum rechts der Isar, Institut für Allgemeine Pathologie und Pathologische Anatomie, München, Germany
3. ³Krankenhaus Lichtenberg, Institut für Pathologie, Berlin, Germany
4. ⁴Technische Universität München, Klinikum rechts der Isar, Institut für Medizinische Statistik und Epidemiologie, München, Germany
5. ⁵Technische Universität München, Klinikum rechts der Isar, Chirurgische Klinik und Poliklinik, München, Germany

Correspondence: Dr B Luber, PhD, Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Trogerstrasse 18, 81675 München, Germany. E-mail: luber@lrz.tu-muenchen.de

^*A Walch and S Seidl contributed equally and share the first authorship.

Received 18 June 2007; Revised 11 December 2007; Accepted 31 December 2007; Published online 1 February 2008.

Abstract

Rho GTPases are a family of major regulators of E-cadherin-mediated cell adhesion that are implicated in the carcinogenic process by deregulated expression of the family members itself or of upstream modulators or downstream effectors. Combined investigation of the Rho GTPase Rac1, the effector protein IQGAP1 and the activator Tiam1 in relation to expression or mutation of E-cadherin in gastric adenocarcinomas has not been reported. The aim of the study was to determine the expression and prognostic significance of Rac1, IQGAP1, Tiam1 and E-cadherin in gastric adenocarcinomas. Gastric carcinomas of 76 patients were investigated immunohistochemically in a tissue microarray study for expression of Rac1, IQGAP1, Tiam1 and E-cadherin. Correlations with clinical and follow-up data were examined. Moderate or strong reactivity for Rac1 was observed in 46% and for Tiam1 in 56% of tumors. Expression of IQGAP1 was present in 59% and of E-cadherin in 87% of tumors. While Rac1 and E-cadherin expression were not related to prognosis, a trend was observed between a lack of IQGAP1 expression (log-rank 0.088) as well as presence of Tiam1 (log-rank 0.097) and favorable prognosis in Kaplan–Meier survival analysis. Expression of Rac1 was positively linked to IQGAP1 expression (P=0.007, r=0.343) and tended to be inversely associated with expression of E-cadherin (P=0.055, r=- 0.245). In conclusion, we observed deregulated expression of Rac1, IQGAP1, Tiam1 and E-cadherin in gastric cancer. We present evidence that either upregulation (for Rac1 and IQGAP1) or downregulation (for Tiam1 and E-cadherin) occurs. Rac1 and E-cadherin expression were not related to prognosis, while trends pointing to favorable prognosis of patients with Tiam1 expression and a lack of IQGAP1 expression were observed. These results indicate that the investigated regulators of E-cadherin-mediated cell adhesion play a role in gastric carcinogenesis.