Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers.

There are many scoring methods evaluating the expression of p16 in the bladder immunohistochemically. In this study our aim was to determine an optimal p16 scoring method by discussing different staining methods related with p16 expression in bladder cancers and to establish the association of p16 and Ki-67 expressions, alone or in combination, with recurrence and progression. Ninety patients undergoing their first transurethral resection for bladder cancer and newly diagnosed papillary urothelial carcinoma (pTa and pT1) were included in the study. Four different scoring methods were used for p16 (p16a, p16b, p16c, p16d). The patients were divided into two groups based on recurrence and progression. There was a statistically significant difference between recurrence and abnormal p16d staining (p = 0.005). In other staining patterns of p16, there was no statistically significant difference in terms of recurrence or progression.In the multivariate logistic regression analysis, combined Ki-67 ≥ 10 and abnormal p16d staining was found to be the only independent predictive factor for recurrence (OR = 2.26, 95% CI: 0.13-46.41, p = 0.035) and no independent predictive factor for progression was found. Determining an adequate expression scoring by taking normal transitional epithelial staining pattern as a reference would be an objective approach in p16 evaluation. Moreover, it was found that evaluating p16d and Ki-67 in combination would be significant in predicting recurrence in pTa and pT1 urothelial carcinomas.

Expression of NOS isoforms in internal spermatic veins of infertile men with varicocele.

Although varicocele is a relatively common entity encountered in the evaluation of infertile men, the exact pathophysiology still remains unclear. Recently, as previously widely investigated in various parts of human circulatory system, nitric oxide synthase (NOS) and its product, nitric oxide (NO) have been thought to play a role in the development of varicocele and thus male infertility. In this study, we determined the concentration of NO metabolite and the expression of NOS isoforms in the internal spermatic (ISV) and superficial branch of inferior epigastric veins of infertile men with varicocele. The study included 60 infertile men with clinically unilateral or bilateral varicocele. Expression of inducible and endothelial NOS (iNOS and eNOS) isoforms were investigated in tissue arrays of internal spermatic and superficial branch of inferior epigastric veins with immunohistochemistry. NO metabolite (nitrite) levels were measured using the calorimetric method. A significantly higher expression of eNOS was observed in the varicose veins (mean score: 2.25 and 1.55, respectively; p = 0.0001). However, statistically, there was no significant difference for expression of iNOS between varicose and control veins (p = 0.094). The nitrite concentration and NOS expression were not found to be correlated with clinical variables (varicocele grade, maximum varicose vein diameter, and sperm concentration, motility, and morphology) (p > 0.05). As a result, the significantly higher expression of eNOS in ISV may be responsible for the development of varicocele, although this finding is not accompanied by an increase in NO concentration. Still, the pattern of the relationship between varicocele and increased eNOS expression warrants further investigation.