RESUMO
Establishment and maintenance of the apical-basal cell polarity, required for proper replication, migration, specialized functions and tissue morphogenesis, relies on three evolutionary conserved complexes: PAR, CRUMBS and SCRIBBLE. Loss of cell polarity/cohesiveness (LOP/C) is implicated in cancer progression, and members of the polarity complex have been described as either oncogenes or oncosuppressors. However, no information on their role in thyroid cancer (TC) progression is available. In the present study, we evaluated the gene expression of the PAR complex members aPKCι, PARD3α/ß and PARD6α/ß/γ in 95 papillary TC (PTC), compared to their normal matched tissues and in 12 anaplastic TC (ATC). The mRNA and protein levels of investigated genes were altered in the majority of PTC and ATC tissues. In PTC, univariate analysis showed that reduced expression of aPKCι, PARD3ß and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3ß mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3ß are independent risk factors for recurrences, with hazard ratio, respectively, of 8.21 (p=0.006) and 3.04 (p=0.029). The latter result was confirmed by the Kaplan-Meier analysis, which evidenced the association between decreased PARD3ß mRNA levels and shorter disease-free interval. In conclusion, we demonstrated that the expression of PAR complex components is deregulated in the majority of PTC and there is a general trend towards their reduction in ATC tissues. Moreover, a prognostic value for the PARD3ß gene in PTCs is suggested.
RESUMO
High or low thyroid-stimulating hormone (TSH) levels seem to be associated with several negative outcomes in the elderly, but the literature about TSH and frailty is still limited. In this article, we investigated whether TSH is associated with prevalent and incident frailty in a cohort of older community-dwelling subjects. Among 3099 initially screened in the Progetto Veneto Anziani Study, 2571 men and women aged ≥65 years (for cross-sectional analyses) and 1732 (longitudinal, mean follow-up period of 4.4 years) were divided into sex-specific quintiles according to baseline serum TSH concentrations within normal range (0.3 and 4.2 mUI/L). Frailty was defined as the presence of three among five Fried's criteria. At baseline, taking those in the third quintile of serum TSH as reference (Q3) and adjusting for potential confounders, participants in the highest (Q5) quintile had an increased odds ratio (OR) of having frailty (OR = 1.55; 95% confidence interval [CI]: 1.03-2.33 for men; OR = 1.97; 95% CI: 1.59-2.45 for women). Men in Q1 had significant higher odds of having muscle weakness and exhaustion, while those in Q5 had muscle weakness and slow gait speed. Women in Q1 had significantly higher odds of having all the Fried's criteria (except for exhaustion), while those in Q5 reported a significantly higher presence of muscle weakness and slow gait speed. At follow-up, men in Q5 had an increased risk of frailty (OR = 1.37; 95% CI: 1.02-1.91) similar to women in Q1 (OR = 1.47; 95% CI: 1.21-1.78). In conclusion, men with higher and women with lower serum TSH levels are at increased risk of frailty.
