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.

• Keywords
• Clear cell carcinoma, Endometrioid carcinoma, HNF-1-beta, Immunohistochemistry, Methylation, Mutation analysis,
• MeSH
• Adenocarcinoma, Clear Cell genetics   pathology   MeSH
• Carcinoma, Endometrioid genetics   pathology   MeSH
• Epigenesis, Genetic genetics   MeSH
• Epigenomics methods   MeSH
• Genetic Variation genetics   MeSH
• Hepatocyte Nuclear Factor 1-beta genetics   MeSH
• Immunohistochemistry methods   MeSH
• Humans MeSH
• DNA Methylation genetics   MeSH
• Biomarkers, Tumor genetics   MeSH
• Endometrial Neoplasms genetics   pathology   MeSH
• Promoter Regions, Genetic genetics   MeSH
• Cystadenocarcinoma, Serous genetics   pathology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hepatocyte Nuclear Factor 1-beta MeSH
• HNF1B protein, human MeSH Browser
• Biomarkers, Tumor MeSH