Leiomyoma with Bizarre Nuclei: a Study of 108 Cases Focusing on Clinicopathological Features, Morphology, and Fumarate Hydratase Alterations

Gregová, Mária; Hojný, J.; Němejcová, Kristýna; Bártů, Michaela; Mára, Michal; Boudova, Barbora; Laco, Ján; Krbal, Lukáš; Tichá, Ivana; Dundr, Pavel

doi:10.1007/s12253-019-00739-5

Cited by 24 publications

(32 citation statements)

References 38 publications

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“…The sequencing was performed either using 50 samples, which were sequenced in one amplicon library by the MiSeq 300 cycles v2 kit or using 90 samples by the NextSeq 300 cycles mid output kit v2.5. The amplicon sequencing approach showed low coverage of 20 bp on the 5′ end of the exon 4 in all of the tested samples, and therefore this part was additionally sequenced by the Sanger sequencing method as we described elsewhere with the use of a specific primer pair (Supplementary Table 3) 67 .…”

Section: Samplesmentioning

confidence: 99%

HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study

Dundr

Bártů

Hojný

et al. 2020

Sci Rep

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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. Hepatocyte nuclear factor 1 beta (HNF1B) is an important tissue specific transcription factor, which is essential for the embryonic development of several organs including the kidney, pancreas, liver, biliary tract, genital tract, and gastrointestinal system 1,2. Heterozygous germline mutations are associated with several congenital diseases of the kidney, pancreas, and urogenital tract, and the role of HNF1B in these diseases is well known 3-5. However, despite the increased awareness that HNF1B plays an important role in the carcinogenesis of several solid tumors, the exact significance of HNF1B in carcinogenesis is not yet fully understood 6-9. The regulatory mechanisms and pathways in which HNF1B is involved in the process of carcinogenesis are not clear, but it appears that HNF1B may act as either oncogene or oncosuppressor gene based on the type of tumor and its histogenesis 6,7,10. In the prostate, an increased expression of HNF1B seems to be protective against prostate cancer, and HNF1B therefore has been attributed an oncosuppressive role 10. However, the levels of protein expression of HNF1B in prostate cancer are not well known, and the mechanisms playing role in its regulation are of interest. According to current knowledge, HNF1B is commonly inactivated in prostate cancer, especially due to HNF1B promoter methylation, which occurs in about 50% of cases 11. Another recently suggested possible mechanisms of HNF1B inactivation is the effect of the enhancer of zeste homolog 2 (EZH2), the overexpression of which has been suggested to downregulate the expression of HNF1B 12,13. EZH2 is a gene belonging to the category of Polycomb

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Section: Samplesmentioning

confidence: 99%

HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study

Dundr

Bártů

Hojný

et al. 2020

Sci Rep

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“…In classical leiomyomas, the expression of immunohistochemical p16 and p53 is rarely seen, whereas the expression of these markers is frequently observed in LBN. 2,7 Even though LBN display benign clinical behavior, their differential diagnosis from leiomyosarcoma can sometimes be difficult. These tumors can be distinguished from leiomyosarcoma by the absence of high mitotic rate and tumor cell necrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Leiomyoma with bizarre nuclei (LBN) is an infrequent variant of uterine smooth muscle neoplasm. 1,2 Although LBN is most commonly defined in the uterus, it has been reported in the literature that to also seen in localizations, such as the vagina, 3 scrotum, 4 renal pelvis, 5 and prostate gland. 6 Herein, we present a very rare case of LBN localized in the paratubal cyst wall.…”

Section: Introductionmentioning

confidence: 99%

Leiomyoma with Bizarre Nuclei (Symplastic Leiomyoma) in the Paratubal Cyst Wall: Report of a Rare Case

Çelik

2021

Int J Surg Pathol

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Leiomyoma is a benign mesenchymal tumor that develops from smooth muscle cells. It can present in various histological variants. Leiomyoma with bizarre nuclei is an infrequent variant of uterine smooth muscle neoplasm. It is characterized by focally or diffusely distributed bizarre cells on the background of a typical leiomyoma. These bizarre cells are large, multinucleated, or multilobulated and have an eosinophilic cytoplasm. Even though leiomyomas with bizarre nuclei display benign clinical behavior, their differential diagnosis from leiomyosarcoma can sometimes be difficult. Leiomyoma has been described most commonly in the uterus. There is no case of leiomyoma originating from paratubal cysts described in the literature. In this article, we present a rare case of leiomyoma with bizarre nuclei originating from a paratubal cyst.

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“…The sequencing was performed either using 50 samples, which were sequenced in one amplicon library by the MiSeq 300 cycles v2 kit or using 90 samples by the NextSeq 300 cycles mid output kit v2.5. Because in all of the tested samples the amplicon sequencing approach showed a low coverage of 20 bp on the 5′-end of exon 4, this part was additionally sequenced by the Sanger sequencing method as described elsewhere 31 with the use of a specific primer pair (Supplementary Table 1).…”

Section: Statistical Analysesmentioning

confidence: 99%

Analysis of expression, epigenetic, and genetic changes of HNF1B in 130 kidney tumours

Bártů

Hojný

Hájková

et al. 2020

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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.

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Leiomyoma with Bizarre Nuclei: a Study of 108 Cases Focusing on Clinicopathological Features, Morphology, and Fumarate Hydratase Alterations

Cited by 24 publications

References 38 publications

HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study

HNF1B, EZH2 and ECI2 in prostate carcinoma. Molecular, immunohistochemical and clinico-pathological study

Leiomyoma with Bizarre Nuclei (Symplastic Leiomyoma) in the Paratubal Cyst Wall: Report of a Rare Case

Analysis of expression, epigenetic, and genetic changes of HNF1B in 130 kidney tumours

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