Arndt Hartmann

Edwin Herrmann

Elke Eltze

Johannes Giedl

Lothar Hertle

Rudolf Moritz

 264  Background: Activation of the mTOR pathway can be observed in various tumor entities. In advanced urothelial carcinoma of the bladder (BCA) its role still is unclear. The aim of our study was to examine activation of the mTOR cascade in BCA and its correlation with survival data. Methods: Tissues from 268 patients undergoing radical cystektomy were collected to assess the diagnostic and prognostic value of mTOR, HIF1-alpha, p4EB-P1, pAKT and VEGF using tissue microarray-based immunohistochemistry. Results: Overexpression of mTOR pathway enzymes is frequently detected for HIF1-alpha (29.8%), pAKT (53.2%), mTOR (43.3%), p4EB-P1 (28.4%) and VEGF (58.5%). Overexpression of pAKT was a significant predictor of progression (PFS) in pT1 (p=0.026) and pT2 (p=0.018) tumors. Overall survival (OAS) was significantly shorter for patients with pT1 (p=0.021) and pT2 (p=0.026) tumors in this subgroup. HIF1-alpha overexpression leads to significant earlier recurrence of BCA following radical cystektomie in the subgroup of pT3 tumors (p=0.046). High levels of mTOR were predictive for cancer related death (p=0.021) in pT2-tumors. Conclusions: Activation of mTOR-pathway, especially pAKT is of prognostic value in patients with advanced BCA and might be useful as a target for future therapies. </jats:p

The role of VEGF/mTOR/AKT pathway in patients with advanced urothelial carcinoma of the bladder cancer.

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