title: Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas.
abstract: Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs).Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections. The immunohistochemical results were correlated with clinicopathological parameters.Results. The overexpression of HER2 was found in 19.6% of the cases and it was associated with high grade tumors with a high mitotic index and phosphorylation of AKT and mTOR. Muscle-invasive tumors presented both cytoplasmic and nuclear losses of PTEN expression. There was no association between HER/AKT/mTOR pathway activation and CAM expression. Although cadherins were often coexpressed, only p-cadherin immunoreactivity was associated with tumor grade and high proliferative index.Conclusions. HER2 overexpression is found in a respective proportion of urothelial carcinomas. P-cadherin expression is associated with high grade UCs but it is not affected by HER2 overexpression or by activation of HER/AKT/mTOR pathway.
authors.affiliation: Urology Department, Interbalkan Medical Center, Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koletsas
authors.affiliation: Pathology Department, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Triantafyllia
authors.identifier: 0000-0002-4435-3532
authors.initials: T
authors.lastname: Koletsa
authors.affiliation: Urology Department, Interbalkan Medical Center, Thessaloniki, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Choidas
authors.affiliation: Laboratory of Biochemistry, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Anagnostopoulos
authors.affiliation: Urology Department, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Touloupidis
authors.affiliation: Pathology Department, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zaramboukas
authors.affiliation: Pathology Department, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Raptou
authors.affiliation: Laboratory of Histology-Embryology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papadopoulos
authors.affiliation: Laboratory of Histology-Embryology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Maria
authors.identifier: 0000-0001-8651-3680
authors.initials: M
authors.lastname: Lambropoulou