We assessed the value of cytokeratin 17 (CK17) expression for the differential diagnosis between primary ovarian mucinous tumors and metastases from the gastrointestinal tract (GIT) and the significance of CK17 expression in a broad spectrum of primary ovarian tumors with respect to their prognosis. The sample set consisted of 554 primary ovarian tumors and 255 GIT tumors. In the primary ovarian tumors, a higher CK17 expression (in > 10% of tumors cells) was present only in 0-11.4% of all tumors (including mucinous tumors, micropapillary serous borderline tumors, clear cell, endometrioid, and high-grade serous carcinomas). The only exception was low-grade serous carcinoma, where higher CK17 expression was present in 24% of cases. Concerning GIT tumors, the higher levels of CK 17 expression (in > 10% of tumor cells) were observed in the upper GIT tumors (68.5% of pancreatic ductal adenocarcinoma, 61.6% of gallbladder adenocarcinoma, and 46% of gastric adenocarcinoma), which differs substantially not only from most of the primary ovarian tumors, but also from colorectal carcinoma (3.7%; p < 0.001). The results of our study suggest that expression of CK17 can potentially be used as an adjunct marker in differential diagnosis between primary ovarian mucinous tumors and metastases from the upper GIT, but not from colorectal carcinoma. However, in GIT tumors, CK17 can be used in the differential diagnosis between adenocarcinomas of the upper and lower GIT. Statistical analysis did not reveal strong association of CK17 expression with clinicopathological variables or patient outcomes in any primary ovarian tumors.

• Klíčová slova
• Cytokeratin 17, Differential diagnosis, Gastrointestinal tract tumors, Ovarian tumors,
• MeSH
• adenokarcinom * diagnóza   MeSH
• diferenciální diagnóza MeSH
• gastrointestinální nádory * diagnóza   MeSH
• imunohistochemie MeSH
• keratin-17 MeSH
• kolorektální nádory * diagnóza   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinivky břišní * diagnóza   MeSH
• nádory vaječníků * patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• keratin-17 MeSH
• nádorové biomarkery MeSH

Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor and putative biomarker of solid tumours. Recently, we have revealed a variety of HNF1B mRNA alternative splicing variants (ASVs) with unknown, but potentially regulatory, functions. The aim of our work was to quantify the most common variants and compare their expression in tumour and non-tumour tissues of the large intestine, prostate, and kidney. The HNF1B mRNA variants 3p, Δ7, Δ7-8, and Δ8 were expressed across all the analysed tissues in 28.2-33.5%, 1.5-2%, 0.8-1.7%, and 2.3-6.9% of overall HNF1B mRNA expression, respectively, and occurred individually or in combination. The quantitative changes of ASVs between tumour and non-tumour tissue were observed for the large intestine (3p, Δ7-8), prostate (3p), and kidney samples (Δ7). Decreased expression of the overall HNF1B mRNA in the large intestine and prostate cancer samples compared with the corresponding non-tumour samples was observed (p = 0.019 and p = 0.047, respectively). The decreased mRNA expression correlated with decreased protein expression in large intestine carcinomas (p < 0.001). The qualitative and quantitative pattern of the ASVs studied by droplet digital PCR was confirmed by next-generation sequencing, which suggests the significance of the NGS approach for further massive evaluation of the splicing patterns in a variety of genes.

• MeSH
• alternativní sestřih * MeSH
• hepatocytární jaderný faktor 1-beta genetika   metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory genetika   metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• protein - isoformy MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• RNA nádorová genetika   metabolismus   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-beta MeSH
• HNF1B protein, human MeSH Prohlížeč
• messenger RNA MeSH
• nádorové biomarkery MeSH
• protein - isoformy MeSH
• RNA nádorová MeSH

High-grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer, with a poor prognosis; however, most studies concerning ovarian carcinoma have focused mainly on clear cell carcinoma. The involvement of hepatocyte nuclear factor 1β (HNF1B) in the carcinogenesis of HGSC has not yet been fully elucidated. To the best of our knowledge, the present study is the first to analyse the expression of the possible downstream target of HNF1B, enoyl-CoA (Δ) isomerase 2 (ECI2), in HGSC. The present study performed a comprehensive analysis of HNF1B mRNA and protein expression, and epigenetic and genetic changes, as well as an analysis of ECI2 mRNA and protein expression in 122 cases of HGSC. HNF1B protein expression was detected in 28/122 cases, and was positively associated with lymphovascular invasion (P=0.025). Protein expression of ECI2 was detected in 115/122 cases, but no associations with clinicopathological variables were revealed. Therefore, ECI2 does not seem to function as a suitable prognostic marker for HGSC. In the sample set, a positive correlation between HNF1B and ECI2 protein expression was detected (P=0.005). HNF1B mRNA was also positively correlated with HNF1B protein expression (P=0.001). HNF1B promoter methylation was detected in 26/67 (38.8%) of cases. A novel pathogenic somatic HNF1B mutation was detected in 1/61 (1.6%) of the analysed HGSC cases. No other correlations between the examined SNPs (rs4430796, rs757210 and rs7405776), HNF1B promoter methylation, HNF1B/ECI2 expression or clinicopathological characteristics were found.

• Klíčová slova
• enoyl-CoA (Δ) isomerase 2, hepatocyte nuclear factor 1β, high-grade serous carcinoma, immunohistochemistry, mRNA, methylation, mutation analysis, ovarian carcinoma,
• Publikační typ
• časopisecké články MeSH

Hepatocyte nuclear factor 1 beta (HNF1B) is a transcription factor which plays a crucial role in nephronogenesis, and its germline mutations have been associated with kidney developmental disorders. However, the effects of HNF1B somatic exonic mutations and its role in the pathogenesis of kidney tumours has not yet been elucidated. Depending on the type of the tumour HNF1B may act as a tumour suppressor or oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using an immunohistochemical approach, and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B in 130 cases of renal tumours (121 renal cell carcinomas, 9 oncocytomas). In the subset of clear cell renal cell carcinoma (ccRCC), decreased HNF1B expression was associated with a higher tumour grade and higher T stage. The mutation analysis revealed no mutations in the analysed samples. Promoter methylation was detected in two ccRCCs and one oncocytoma. The results of our work on a limited sample set suggest that while in papillary renal cell carcinoma HNF1B functions as an oncogene, in ccRCC and chRCC it may act in a tumour suppressive fashion.

• MeSH
• epigeneze genetická genetika   MeSH
• epigenomika metody   MeSH
• hepatocytární jaderný faktor 1-beta genetika   MeSH
• karcinom z renálních buněk genetika   patologie   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• mutační analýza DNA metody   MeSH
• nádory ledvin genetika   patologie   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• zárodečné mutace genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-beta MeSH
• HNF1B protein, human MeSH Prohlížeč

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