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Expression, Epigenetic and Genetic Changes of HNF1B in Endometrial Lesions

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Pathology & Oncology Research

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.

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Acknowledgments

This work was supported by Ministry of Health, Czech Republic (IGA MZ CR project NT14001-3/2013 and RVO-VFN 64165), by Charles University in Prague (Project PRVOUK-P27/LF1/1, UNCE 204024, and SVV UK 260148/2015), by Bank of Biological Material project BBM LM2010004, and by OPPK (Research Laboratory of Tumor Diseases, CZ.2.16/3.1.00/24509).

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Authors and Affiliations

  1. Department of Pathology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Studnickova 2, 2 12800, Prague, Czech Republic

    Kristýna Němejcová, Ivana Tichá & Pavel Dundr

  2. Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, General University Hospital, Charles University in Prague, Prague, Czech Republic

    Petra Kleiblová

  3. Institute of Biology and Medical Genetics, First Faculty of Medicine, General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic

    Petra Kleiblová

  4. First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    Michaela Bártů

  5. 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

    David Cibula

  6. Bank of Biological Material, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    Kateřina Jirsová

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  1. Kristýna Němejcová
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Correspondence to Pavel Dundr.

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Němejcová, K., Tichá, I., Kleiblová, P. et al. Expression, Epigenetic and Genetic Changes of HNF1B in Endometrial Lesions. Pathol. Oncol. Res. 22, 523–530 (2016). https://doi.org/10.1007/s12253-015-0037-2

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  • DOI: https://doi.org/10.1007/s12253-015-0037-2

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