Expression, Epigenetic, and Genetic Changes of HNF1B in Colorectal Lesions: an Analysis of 145 Cases
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ORIGINAL ARTICLE
Expression, Epigenetic, and Genetic Changes of HNF1B in Colorectal Lesions: an Analysis of 145 Cases Michaela Bártů 1 & Jan Hojný 1 & Nikola Hájková 1 & Romana Michálková 1 & Eva Krkavcová 1 & Karol Simon 2 & Vladimír Frýba 3 & Ivana Stružinská 1 & Kristýna Němejcová 1 & Pavel Dundr 1 Received: 10 January 2020 / Accepted: 21 May 2020 # Arányi Lajos Foundation 2020
Abstract 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. Keywords Colon . Adenoma . HNF-1-beta . Immunohistochemistry . Mutation analysis . Methylation
Introduction Hepatocyte nuclear factor 1 beta (HNF1B), also known as Transcription Factor-2 (TCF2), is a member of a family of transcription factors which, primarily, plays a crucial role in the regulation of the development of various tissues and organs. Most importantly, it is implicated in the ontogenesis and
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12253-020-00830-2) contains supplementary material, which is available to authorized users. * Pavel Dundr [email protected] 1
Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studnickova 2, 12800 Prague 2, Czech Republic
2
First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic
3
1st Department of Surgery - Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital, 12808 Prague, Czech Republic
differentiation of the liver (hence its name), but also the lung, gonads, biliary system, kidney and pancreas [1]. In adults, HNF1B expression is found especially in tubule-forming epithelial tissues such as kidney or pancreatic exocri
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