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The clear cell (CCC), high grade serous (HGSC) and endometrioid (EC) ovarian carcinomas share overlapping histological features. The oncogene IMP3 is implicated in CCC with an elusive utility in differential diagnosis. We collected 366 cases with ovarian primary carcinomas to detect IMP3, Napsin-A and HNF-1β by immunochemistry. In 351 cases, the positive expression rate of IMP3 in CCC was significantly higher than that either in EC or HGSC ( p  < 0.01). The sensitivity of IMP3 in CCC was higher than Napsin-A but lower than HNF-1β ( p  < 0.01). The specificity of IMP3 in CCC was lower than Napsin-A but higher than HNF-1β ( p  < 0.01). The composite markers Napsin-A+/IMP3+ and the IMP3+/HNF-1β+/Napsin-A+ offered the highest odds ratio ( p  < 0.001), the highest specificity, the highest positive predictive value and the highest positive likelihood ratio. The ROC analysis showed that the combination of Napsin-A, HNF-1β and IMP3 offered the biggest AUC compared with either the singular marker performances or the other binary combinations ( p  < 0.001). In 15 cases of EC mixed with CCC, IMP3 showed a better discrimination value than the other two markers. Consequently, adding IMP3 to the diagnostic panel might provide some help with the pathological diagnosis of ovarian CCC. [ABSTRACT FROM AUTHOR]

Abstract: Aims/hypothesis: The aim of this study was to investigate clinical spectrum of hepatocyte nuclear factor-1β (HNF-1β) mutation in Chinese diabetic patients with renal dysfunction and/or structure abnormalities. Materials and methods: A total of 104 diabetic patients with renal structural abnormalities and/or non-diabetic renal dysfunction were recruited and HNF-1β mutation was screened by direct sequencing. Results: Three heterozygous missense mutations including c.494G>A (p.R165H), c.662A>T (p.D221V) and c.780G>C (p.E260D) were identified. Progression of diabetes and mild decline of renal function were observed in the mutation carriers during the follow-up. The p.R165H mutation carrier had severe β-cell dysfunction and different extrapancreatic phenotypes. Compared with type 2 diabetes and normoglycemics, the p.R165H mutation carrier had a lower basal C-peptide (0.30, 0.61±0.07 and 0.50±0.04nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively) and low values of acute C-peptide response to arginine (0.15, 0.48±0.18 and 0.76±0.08nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively). Conclusion: Patients with the HNF-1β mutation in our population can have different pancreatic and extrapancreatic phenotypes. The exact contributions of mutations to the phenotypes await functional confirmation. [Copyright &y& Elsevier]

Abstract: The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4α, HNF-1α, and HNF-1β, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3). Nature 384, 455–458; Yamagata, K., Furuta, H., Oda, N., Kaisaki, P.J., Menzel, S., Cox, N.J., et al., 1996b. Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1). Nature 384, 458–460; Horikawa, Y., Iwasaki, N., Hara, M., Furuta, H., Hinokio, Y., Cockburn, B.N. et al., 1997. Mutation in hepatocyte nuclear factor-1β gene (TCF2) associated with MODY. Nat. Genet. 17, 384–385]. Among these transcription factors, the pattern of HNF-4α expression during pancreatic differentiation remains largely unknown. We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1α and HNF-1β. We found considerable variation in the level of HNF-4α expression by the individual epithelial cells in the pancreatic buds on E9.5. HNF-4α and HNF-1β were initially expressed by Pdx1+ common progenitor cells and neurogenin3+ (Ngn3+) endocrine precursor cells during the first transition, but expression of HNF-1β and either HNF-4α or HNF-1α became complementary around the end of the second transition (E15.5). In the mature pancreas, HNF-4α was expressed by glucagon-positive α-cells, insulin-positive β-cells, somatostatin-positive δ-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. Most of the HNF-4α+ cells were also positive for HNF-1α, but HNF-4α expression in some non-β-cells was remarkably high, and this was not paralleled by high HNF-1α expression. These results indicate that the expression of MODY proteins in each of the pancreatic cell types is strictly regulated in accordance with the status of differentiation during pancreatic organogenesis. [Copyright &y& Elsevier]

: BackgroundIn Hong Kong, the prevalence of diabetes is estimated to be 2% in the young population. In the diabetic population, 30% of patients have diagnosis before the age of 40 years. Besides, 30% of young diabetic patients have varying degrees of albuminuria . Mutations in the gene encoding the hepatocyte nuclear factor (HNF)-1β are associated with a subtype of maturity-onset diabetes of the young (MODY 5) characterized by urogenital abnormalities. We examined 74 unrelated Chinese subjects with young-onset diabetes complicated by nephropathy for variants in this gene.: MethodsThe HNF-1β gene was screened by direct sequencing and the functional properties of wild-type and mutant proteins were analyzed by transactivation analysis.: ResultsA novel variant in exon 3 (E260D) was found in one patient. Extended family analysis revealed four other siblings carrying this variant. One subject had diabetes and another had impaired glucose tolerance. Another sibling had microalbuminuria but normal glucose tolerance. Transfection studies showed insignificant differences in transactivation ability between wild-type and mutated HNF-1β. A silent polymorphism Q378Q was identified in another unrelated subject.: ConclusionsThese results suggest genetic variants in HNF-1β are not a common cause of young-onset diabetes or diabetic nephropathy in Chinese, but may modify disease manifestation and progression. Other potential candidate genes should be looked for to account for the high prevalence of young-onset diabetes and nephropathy in this population. [Copyright &y& Elsevier]

Background/Aims: The portal tracts contain bile ducts associated with branches of the portal vein and of the hepatic artery. Hepatic artery malformations are found in diseases in which fetal biliary structures persist after birth (ductal plate malformations). Here we investigated how hepatic artery malformations relate to abnormal bile duct development.Methods: Hepatic artery and biliary development was analyzed in fetuses with Jeune syndrome or Meckel syndrome, which show ductal plate malformations. We also analyzed hepatic artery development in transgenic mice which exhibit biliary anomalies following inactivation of the genes for hepatocyte nuclear factor (HNF)-6 or HNF-1β, two transcription factors expressed in biliary cells, but not in arteries.Results: We show that arterial anomalies occurred in fetuses with Jeune syndrome or Meckel syndrome. We provide the first description of hepatic artery branch development in the mouse and show that inactivation of the Hnf6 or Hnf1β gene results in anomalies of the hepatic artery branches. In the transgenic mice and in the human syndromes, the biliary anomalies preceded the arterial anomalies.Conclusions: A primary defect in biliary epithelial cells is associated with hepatic artery malformations in mice. Our data provide a model to interpret and study hepatic artery anomalies in humans. [Copyright &y& Elsevier]