Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

Kato, Noriko; Sasou, Shunichi; Motoyama, Teiichi

doi:10.1038/modpathol.3800492

Cited by 208 publications

(176 citation statements)

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“…Among them, hepatocyte nuclear factor 1 beta (HNF1b) seems to be the best because of its high sensitivity and specificity. 32,33 However, one study reported HNF1b positivity in the nuclei of normal and tumor cells in the endometrium, 34 and the establishment of other markers may also be useful for differential diagnosis of clear cell adenocarcinoma. Annexin-A4, 35,36 HOXA10, 37 phospho-serine aminotransferase, 36 and glypican 3 38 are all suitable candidates.…”

Section: Discussionmentioning

confidence: 99%

“…However, five of the eight cases with both endometriosis and clear cell adenocarcinoma, the atypical and normallooking epithelium at the surface of the endometriotic cysts showed at least focal napsin A positivity. As positive expression of HNF1b is reported in the nuclei of the epithelial cells in the majority of the cases with endometriosis, 33 it is possible that napsin A may have a different role than HNF1 b in ovarian clear cell adenocarcinoma tumor cells. However, further analysis using more cases is necessary for clarification.…”

Section: Discussionmentioning

confidence: 99%

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Napsin A is a specific marker for ovarian clear cell adenocarcinoma

et al. 2015

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Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

et al. 2015

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“…11 It was also subsequently reported to be positive in areas of endometriosis or endometriotic epithelium in a study of ovarian clear cell carcinoma lending molecular support for the hypothesis that the concurrent endometriosis seen in ovarian clear cell carcinoma may be linked as a precursor lesion. 12 The significance of clear cell carcinoma as an entity in pancreatic cancers is inadequately characterized. Our study of 84 archived cases of diagnosed pancreatic adenocarcinomas has uncovered the largest known report of a clear cell phenotype consisting of at least 75% of the tumor.…”

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confidence: 99%

Clear cell carcinoma of the pancreas: histopathologic features and a unique biomarker: hepatocyte nuclear factor-1β

et al. 2008

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Clear cell carcinoma as a variant of ductal carcinoma of the pancreas is not well recognized. Hepatocyte nuclear factor-1b as a transcription factor has been identified as a specific biomarker of clear cell tumor of the female genital tract. The aim of this study was to systematically analyze clear cell carcinoma of the pancreas and its unique biomarker hepatocyte nuclear factor-1b. A total of 84 pancreatic adenocarcinomas were analyzed pathologically and with an immunohistochemical approach with hepatocyte nuclear factor-1b antibody. The identified clear cell carcinomas were further studied by PAS, DPAS, and mucicarmine stains. Pathologic features and clinical follow-up were documented. Of them, 20 (24%) pancreatic adenocarcinomas were identified with clear cell features, including 12 clear cell carcinomas and 8 ductal adenocarcinomas with clear cell component (defined as less than 75% of tumor with clear cells). Cytologically, the clear cell carcinomas exhibited clear cytoplasm with centrally located, atypical nuclei. PAS, DPAS, and mucicarmine stains confirmed that the clear cytoplasm was not due to accumulation of glycogen or mucin. The results of immunostaining showed that hepatocyte nuclear factor-1b is overexpressed in all clear cell carcinomas and in the clear cell components of eight ductal carcinomas with clear cell features. In contrast, in usual ductal adenocarcinoma, hepatocyte nuclear factor-1b exhibited overall weak or focally moderate staining; only eight cases were strongly positive (15%) of which 38% were high grade and 63% were moderate grade. However, when included with the strong staining cases in mixed and clear cell carcinoma, this group regardless of morphology appeared to correlate with worse survival compared to the group with weak hepatocyte nuclear factor-1b staining across morphologies (Po0.01). Thus, clear cell carcinoma of the pancreas is not an uncommon variant of pancreatic ductal adenocarcinoma. Hepatocyte nuclear factor-1b is a useful marker to identify these clear cell carcinomas, and its overexpression may aid in stratifying survival rate.

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“…Their POU S domains have at least one additional α-helix at the N-terminus, and the second † This work was funded by the Juvenile Diabetes Research Foundation (1-2004-506) (8,24). Recently, HNF1β has also been associated with ovarian clear cell carcinoma (25,26), and mutations in this protein are also responsible for neonatal cholestatic jaundice (27). Thus, in addition to its effect on pancreatic β-cells (5,28,29), HNF1β appears to be involved in normal functioning of many other organs (10,11).…”

Section: Introductionmentioning

confidence: 99%

“…Even though mutations in both are associated with diabetes, renal developmental disorders and genital malformations are more prominent with the mutations in HNF1β (7,8), which also encompass a wide clinical spectrum including genital tract malformations, abnormal liver function, pancreatic atrophy, exocrine insufficiency, and biliary manifestations (8,24). Recently, HNF1β has also been associated with ovarian clear cell carcinoma (25,26), and mutations in this protein are also responsible for neonatal cholestatic jaundice (27). Thus, in addition to its effect on pancreatic β-cells (5,28,29), HNF1β appears to be involved in normal functioning of many other organs (10,11).…”

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confidence: 99%

Structural Basis of Disease-Causing Mutations in Hepatocyte Nuclear Factor 1β^,

2007

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HNF1β is an atypical POU transcription factor that participates in a hierarchical network of transcription factors controlling the development and proper function of vital organs such as liver, pancreas, and kidney. Many inheritable mutations on HNF1β are the monogenic causes of diabetes and several kidney diseases. To elucidate the molecular mechanism of its function and the structural basis of mutations, we have determined the crystal structure of human HNF1β DNA binding domain in complex with a high-affinity promoter. Disease-causing mutations have been mapped to our structure, and their predicted effects have been tested by a set of biochemical/ functional studies. These findings together with earlier findings with a homologous protein HNF1α, help us to understand the structural basis of promoter recognition by these atypical POU transcription factors and the site-specific functional disruption by disease-causing mutations.HNF1β (hepatocyte nuclear factor 1β; also known as vHNF1 or TCF2) is a widely distributed transcription factor that plays a critical role in early vertebrate development and embryonic survival (1-3). First identified as a key regulator in the liver, HNF1β is also expressed in the pancreas, kidney, lung, ovary, testis, and throughout the gastrointestinal tract. In pancreatic β-cells, HNF1β is known to form an integrated regulatory network with other transcription factors such as HNF1α, HNF4α, Pdx-1, Foxa2, and NeuroD1 for organ development and proper function (1,4). Thus, in humans, heterozygous mutations in the HNF1β gene have been linked to neonatal diabetes (5) and the autosomal dominant subtype of diabetes known as MODY (maturity-onset diabetes of the young) (6). Extrapancreatic diseases are also increasingly recognized in different organs, especially in the kidney, with a variety of renal developmental disorders such as renal cysts, familial hypoplastic glomerulocystic kidney disease, renal malformation, and atypical familial hyperuricaemic nephropathy (7-11).POU transcription factors, which include Pit-1, Oct-1, and Unc-86 as founding members and are now expanded to more than 13 members in humans, are developmental regulators of various neuroendocrine organs, and their sequence-specific DNA binding is mediated by a bipartite motif that consists of a POU homeodomain (POU H ) and POU-specific domain (POU S ) (12,13). POU H is a 60 amino acid classic homeodomain made of three α-helices with the third as a DNA recognition helix, while POU S is an additional ∼75 amino acid all-α-helical motif that cooperates with POU H to enhance the binding affinity and specificity of DNA binding ( Figures 1 and 2) (12,14). HNF1α (MODY3 gene product, the most commonly mutated MODY protein) and HNF1β (MODY5 gene product) are atypical members of the POU transcription factors. Their POU S domains have at least one additional α-helix at the N-terminus, and the second † This work was funded by the Juvenile Diabetes Research Foundation (1-2004-506) (8,24). Recently, HNF1β has also been associated wi...

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Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

Cited by 208 publications

References 16 publications

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

Clear cell carcinoma of the pancreas: histopathologic features and a unique biomarker: hepatocyte nuclear factor-1β

Structural Basis of Disease-Causing Mutations in Hepatocyte Nuclear Factor 1β^,

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Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

Cited by 208 publications

References 16 publications

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

Clear cell carcinoma of the pancreas: histopathologic features and a unique biomarker: hepatocyte nuclear factor-1β

Structural Basis of Disease-Causing Mutations in Hepatocyte Nuclear Factor 1β,

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Structural Basis of Disease-Causing Mutations in Hepatocyte Nuclear Factor 1β^,