Hepatocyte 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. Hepatocyte nuclear factor 1 beta (HNF1B) is an important tissue specific transcription factor, which is essential for the embryonic development of several organs including the kidney, pancreas, liver, biliary tract, genital tract, and gastrointestinal system 1,2. Heterozygous germline mutations are associated with several congenital diseases of the kidney, pancreas, and urogenital tract, and the role of HNF1B in these diseases is well known 3-5. However, despite the increased awareness that HNF1B plays an important role in the carcinogenesis of several solid tumors, the exact significance of HNF1B in carcinogenesis is not yet fully understood 6-9. The regulatory mechanisms and pathways in which HNF1B is involved in the process of carcinogenesis are not clear, but it appears that HNF1B may act as either oncogene or oncosuppressor gene based on the type of tumor and its histogenesis 6,7,10. In the prostate, an increased expression of HNF1B seems to be protective against prostate cancer, and HNF1B therefore has been attributed an oncosuppressive role 10. However, the levels of protein expression of HNF1B in prostate cancer are not well known, and the mechanisms playing role in its regulation are of interest. According to current knowledge, HNF1B is commonly inactivated in prostate cancer, especially due to HNF1B promoter methylation, which occurs in about 50% of cases 11. Another recently suggested possible mechanisms of HNF1B inactivation is the effect of the enhancer of zeste homolog 2 (EZH2), the overexpression of which has been suggested to downregulate the expression of HNF1B 12,13. EZH2 is a gene belonging to the category of Polycomb

Summary Background It has been shown that decreased expression and activity of extracellular matrix protein mindin correlate with various types of cancers including breast, colon and lung cancers. The aim of the presented study was to investigate the serum mindin levels in prostate cancer. Methods Mindin concentrations in serum were measured in 56 patients with prostate cancer (mean age 68 years) and in control group of 29 healthy men (mean age 64 years) using commercially available enzymatic immunoassay (Cusabio, WuHan, China). The patients were divided with respect to the severity of the disease into two groups according to the EAU guidelines (stage 1, 2 – less severe tumours, stage 3, 4 – severe tumours). Results Serum mindin concentrations were significantly elevated in the group of healthy individuals unlike in the patients with prostate cancer (2.12 ng/mL vs 0.78 ng/mL, with P=0.0007, AUC=0.705). Patients with less severe tumours (stage 1, 2) and severe tumours (stage 3, 4) had significantly decreased levels of S-mindin as well (P=0.0037), although the difference in serum mindin concentrations between the patients with less severe and severe tumours was not significant. Conclusions Concentrations of mindin were decreased in patients with prostate cancer and reduced in patients with less severe prostate cancer as well. Mindin appears to be a promising diagnostic marker useful in the diagnosis of prostate cancer.

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