Aims Dedifferentiated endometrial carcinoma (DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 (BRG1) and SMARCB1 (INI1) were recently described as potential mechanisms underlying the histologic dedifferentiation. The aim of this study is to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histologic and molecular features (BRG1/INI1-deficiency). Methods and results We evaluated PAX8, estrogen receptor (ER) and p53 immunostaining in the endometrioid and the undifferentiated components of 20 BRG1/INI1-deficient DDECs and 15 BRG1/INI1-intact DDECs, and compared the results to that of 23 grade 3 endometrioid carcinomas. The differentiated endometrioid component was positive for PAX8 and/or ER in 19 of 20 BRG1/INI1-deficient DDECs while the corresponding undifferentiated component of all 20 tumors showed a complete absence of PAX8 and ER staining. All except one of the BRG1/INI1-deficient tumors displayed a wild-type p53 staining pattern. PAX8 and ER expression in the undifferentiated component was absent in 67% and 80% of BRG1/INI1-intact DDECs respectively, while 47% of the BRG1/INI1-intact DDECs showed mutated p53 staining pattern. In comparison, absent PAX8 and ER expression were each observed in the more solid area of 48% and 48% of grade 3 endometrioid carcinomas. Conclusions The consistent absence of PAX8 and ER expression in molecularly defined (BRG1/INI1-deficient) DDECs suggest that the loss of PAX8 and ER expression is a fundamental feature of dedifferentiation. The frequent findings of mutated p53 staining pattern in BRG1/INI1-intact DDECs indicate that BRG1/INI1-intact DDECs may be biologically different from BRG1/INI1-deficient tumors.

a b s t r a c tGeriatric frailty has drawn growing interest in recent years for its associations with multiple adverse outcomes. Previous studies showed that interventions may improve some aspects of frailty such as physical function. However, interventions targeting the entire frailty construct have not been systemically reviewed. We conducted a comprehensive search for randomized controlled trials targeting geriatric frailty. Only trials that measured outcomes based on their predefined frailty indicators were included. Of 98 articles, 11 met the inclusion criteria. Eight studies were classified as high quality. Of the six exercise-based interventions, five showed significant improvements on at least two of their frailty indicators. Hormone replacement therapy was not effective. Two of the three multifactorial interventions have not published their results, and the third did not show significant improvements. More studies with standardized definitions and measurements of frailty are needed to determine the effectiveness of interventions on geriatric frailty.

BackgroundSelenium is an essential micronutrient known for its antioxidant function. However, the association of serum selenium with lipid profiles and fasting glucose are inconsistent in populations with average intake of selenium. Furthermore, there were few studies conducted specifically for the elderly. This study examined the relationship of serum selenium concentration with serum lipids and fasting glucose in the Taiwanese elderly population.MethodsThis was a cross-sectional study of 200 males and females aged 65-85 years (mean 71.5 ± 4.6 years) from Taipei, Taiwan. Serum selenium was measured by inductively coupled plasma-mass spectrometer. The association between serum selenium and metabolic factors was examined using a multivariate linear regression analysis after controlling several confounders.ResultsThe mean serum selenium concentration was 1.14 μmol/L, without significant difference between sexes. Total cholesterol, triglycerides, and LDL cholesterol increased significantly with serum selenium concentration (P < 0.001, P < 0.05 and P < 0.001, respectively) after adjusting for age, gender, anthropometric indices, lifestyle factors, and cardio-vascular risk factors in several linear regression models. Furthermore, there was a significantly positive association between serum selenium and serum fasting glucose concentrations (P < 0.05).ConclusionsTotal cholesterol, triglycerides, and LDL cholesterol, and fasting serum glucose concentrations increased significantly with serum selenium concentration in the Taiwanese elderly. The underlying mechanism warrants further research.