Author:
Dundr Pavel,Bártů Michaela,Hojný Jan,Michálková Romana,Hájková Nikola,Stružinská Ivana,Krkavcová Eva,Hadravský Ladislav,Kleissnerová Lenka,Kopejsková Jana,Hiep Bui Quang,Němejcová Kristýna,Jakša Radek,Čapoun Otakar,Řezáč Jakub,Jirsová Kateřina,Franková Věra
Abstract
AbstractHepatocyte nuclear factor 1 beta (HNF1B) is a tissue specific transcription factor, which seems to play an important role in the carcinogenesis of several tumors. In our study we focused on analyzing HNF1B in prostate carcinoma (PC) and adenomyomatous hyperplasia (AH), as well as its possible relation to the upstream gene EZH2 and downstream gene ECI2. The results of our study showed that on an immunohistochemical level, the expression of HNF1B was low in PC, did not differ between PC and AH, and did not correlate with any clinical outcomes. In PC, mutations of HNF1B gene were rare, but the methylation of its promotor was a common finding and was positively correlated with Gleason score and stage. The relationship between HNF1B and EZH2/ECI2 was equivocal, but EZH2 and ECI2 were positively correlated on both mRNA and protein level. The expression of EZH2 was associated with poor prognosis. ECI2 did not correlate with any clinical outcomes. Our results support the oncosuppressive role of HNF1B in PC, which may be silenced by promotor methylation and other mechanisms, but not by gene mutation. The high expression of EZH2 (especially) and ECI2 in PC seems to be a potential therapeutic target.
Funder
Ministerstvo Zdravotnictví Ceské Republiky
Univerzita Karlova v Praze
European Regional Development Fund
Publisher
Springer Science and Business Media LLC