PURPOSE: Vav3 is a guanine nucleotide exchange factor that regulates the activity of Rho/Rac family GTPases. In a study on ovarian cancer, we recently demonstrated pronounced prognostic and predictive value of Vav3.1, a specific truncation variant of the parental Vav3 gene. Here, we sought to investigate the role of Vav3.1 in the most prevalent gynecological tumor entity, endometrial cancer. METHODS: Vav3.1 transcript levels were determined in a large cohort of endometrial cancer patients using variant-specific PCR (n = 239), and non-malignant endometrial tissue served as control (n = 26). Expression levels of Vav3.1 were stratified according to established clinicopathological characteristics and correlated to long-term patient survival (average follow-up of > 7.5 years). Type 1 and type 2 cancers were separately investigated. RESULTS: While Vav3.1 was markedly overexpressed in endometrial cancer tissue, we could not detect associations with clinical parameters related to prognosis, such as FIGO stage and tumor grade. Kaplan-Meier estimators of different measures of survival failed to show prognostic significance of Vav3.1 in endometrial cancer. Lack of prognostic value was observed for both type 1 and type 2 cancers. CONCLUSIONS: Our study shows that Vav3.1 is not suited as a marker of cancer progression and/or treatment response in endometrial cancer. Feasibility and potential benefit of targeting Vav3.1 in endometrial cancer needs to be evaluated in future studies, proceeding from its clear, roughly ten-fold, induction in the malignant endometrium.

Department of Biology and Biomedical Centre Faculty of Medicine Pilsen Charles University Prague 30100 Pilsen Czech Republic

Department of Gynecology and Obstetrics Medical University of Innsbruck Anichstrasse 35 6020 Innsbruck Austria

Internal Medicine 5 Medical University of Innsbruck 6020 Innsbruck Austria

Lungenzentrum Kantonsspital St Gallen Rorschacherstrasse 95 9007 St Gallen Switzerland

Medical Clinic 3 Oncology Hematology and Rheumatology University Clinic Bonn 53127 Bonn Germany

Oncotyrol Center for Personalized Cancer Medicine GmbH 6020 Innsbruck Austria

Tyrolean Cancer Research Institute 6020 Innsbruck Austria

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