title: Expression, Epigenetic and Genetic Changes of HNF1B in Endometrial Lesions.
abstract: 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.
authors.affiliation: Department of Pathology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Studnickova 2, 2 12800, Prague, Czech Republic.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Němejcová
authors.affiliation: Department of Pathology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Studnickova 2, 2 12800, Prague, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Tichá
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, General University Hospital, Charles University in Prague, Prague, Czech Republic.|Institute of Biology and Medical Genetics, First Faculty of Medicine, General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleiblová
authors.affiliation: First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Bártů
authors.affiliation: Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Studnickova 2, 2 12800, Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Cibula
authors.affiliation: Bank of Biological Material, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Jirsová
authors.affiliation: Department of Pathology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Studnickova 2, 2 12800, Prague, Czech Republic. pdundr@seznam.cz.
authors.forename: Pavel
authors.initials: P
authors.lastname: Dundr
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics / Q000379:methods; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta
keywords: Clear cell carcinoma; Endometrioid carcinoma; HNF-1-beta; Immunohistochemistry; Methylation; Mutation analysis