Hepatocyte nuclear factor 1 beta (HNF1B) is transcription factor which plays a crucial role in the regulation of the development of several organs, but also seems to be implicated in the development of certain tumours, especially the subset of clear cell carcinomas of the ovary and kidney. Depending on the type of the tumour, HNF1B may act as either a tumour suppressor or an oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using immunohistochemical approach and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B on 40 cases of colorectal adenomas and 105 cases of colorectal carcinomas. The expression of HNF1B was correlated with the benign or malignant behaviour of the lesion, given that carcinomas showed significantly lower levels of expression compared to adenomas. In carcinomas, lower levels of HNF1B expression were associated with recurrence and shortened disease-free survival. The mutation analysis revealed three somatic mutations (two frameshift and one nonsense) in the carcinoma sample set. Promoter methylation was detected in three carcinomas. These results suggest that in colorectal cancer, HNF1B may play a part in the pathogenesis and act in a tumour suppressive fashion.

• Klíčová slova
• Adenoma, Colon, HNF-1-beta, Immunohistochemistry, Methylation, Mutation analysis,
• MeSH
• epigeneze genetická * MeSH
• hepatocytární jaderný faktor 1-beta genetika   MeSH
• kolorektální nádory genetika   metabolismus   patologie   MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   metabolismus   patologie   MeSH
• metylace DNA * MeSH
• míra přežití MeSH
• nádorové biomarkery genetika   MeSH
• následné studie MeSH
• prognóza MeSH
• promotorové oblasti (genetika) MeSH
• regulace genové exprese u nádorů * MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-beta MeSH
• HNF1B protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH

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.

• MeSH
• enoyl-CoA-izomeráza genetika   metabolismus   MeSH
• EZH2 protein genetika   metabolismus   MeSH
• hepatocytární jaderný faktor 1-beta genetika   metabolismus   MeSH
• hyperplazie prostaty genetika   metabolismus   patologie   MeSH
• imunohistochemie metody   MeSH
• kohortové studie MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• metylace DNA MeSH
• mutace MeSH
• nádory prostaty genetika   metabolismus   patologie   MeSH
• prognóza MeSH
• promotorové oblasti (genetika) MeSH
• prostata patologie   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ECI2 protein, human MeSH Prohlížeč
• enoyl-CoA-izomeráza MeSH
• EZH2 protein, human MeSH Prohlížeč
• EZH2 protein MeSH
• hepatocytární jaderný faktor 1-beta MeSH
• HNF1B protein, human MeSH Prohlížeč
• messenger RNA MeSH

Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group. We detected expression of HNF-1-beta in 28 % of ECs (51/180 cases), 26 % of serous carcinoma (7/27 cases), 83 % of endometrial clear cell carcinoma (15/18 cases), 93 % of hyperplastic polyps with atypias (13/14 cases), 100 % of hyperplastic polyps without atypias (16/16 cases), 88 % of hyperplasias with atypias (14/16 cases), 91 % of hyperplasias without atypias (10/11 cases), and in ≥80 % of different normal endometrium samples. The control group of OCCCs showed HNF-1-beta expression in 95 % (18/19 cases). Methylation in promoter region was detected in 13.3 % (4/30) of ECs, but not in corresponding normal tissue where available, nor in OCCCs (0/15 cases). Mutation analysis revealed truncating variant c.454C > T (p.Gln152X) in one EC and missense variant c.848C > T (p.Ala283Val) was detected in one OCCC. In conclusion, expression of HNF-1-beta was detected in various extents in all types of lesions analyzed, nevertheless its strong expression was mostly limited to clear cell carcinomas. Biological significance of genetic and epigenetic changes needs further investigation.

• Klíčová slova
• Clear cell carcinoma, Endometrioid carcinoma, HNF-1-beta, Immunohistochemistry, Methylation, Mutation analysis,
• MeSH
• adenokarcinom z jasných buněk genetika   patologie   MeSH
• endometroidní karcinom genetika   patologie   MeSH
• epigeneze genetická genetika   MeSH
• epigenomika metody   MeSH
• genetická variace genetika   MeSH
• hepatocytární jaderný faktor 1-beta genetika   MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory endometria genetika   patologie   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• serózní cystadenokarcinom genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-beta MeSH
• HNF1B protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH