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The clinical management of tumor patients is often strongly influenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using κ statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by κ values ranging from 0.24 to 0.74 (mean κ = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean κ = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.

Presence of T2 and higher-stage tumors, high-grade tumors, and multifocality are combined risk factors for urinary bladder recurrence and distant organ metastasis. Patients with the additional risk factors of cigarette smoking (urinary bladder recurrence) and nodal disease (distant organ metastasis) should be followed up closely after surgery.

The aim of this study is to detect the expression levels of spindle assembly checkpoint protein-BubR1 and microtubule-associated protein-Tau in human prostate cancer tissues of different Gleason score, and to test whether there is a relationship between their expression levels and clinicopathologic parameters including response to docetaxel treatment, Gleason score, and overall survival (OS). Moreover, to test whether Tau protein expressed in the cancerous prostate tissue is phosphorylated. Thirty patients who received at least three cycles docetaxel for metastatic castrate-resistant prostate cancer were included into the trial. The patients' formalin-fixed and paraffin-embedded prostate tissue specimens were retrospectively obtained from the pathology department archives of Ege University School of Medicine. The expression status of BubR1 protein was defined by immunohistochemical (IHC) using the anti-BubR1 antibody. The expression status of Tau protein was defined by IHC using the two types of Tau antibodies: anti-Tau-1 antibody (that recognizes Tau only in its dephosphorylated form) and anti-PHF-Tau antibody (that recognizes all isoforms of human Tau proteins independent of its phosphorylation status). The BubR1 and Tau were overexpressed in about 63 and 23 % of the study group, respectively. Tau overexpression was significantly associated with lower Gleason score. There was no significant association between the expression levels of BubR1 and Tau proteins, and docetaxel response. Reduced BubR1 expression was strongly associated with longer survival (P = 0.008), whereas Tau expression status did not effect survival. Moreover, the Tau expression of cancerous prostate tissue was highly dephosphorylated. In this clinicopathological study, our findings did not confirm the preclinical observations that low BubR1 and Tau expression confer selective sensitivity to microtubulisin drugs. Our data imply that reduced BubR1 expression was a predictor for longer OS, and the possibility that high Tau expression may be involved in better prognosis due to its relationship to the Gleason score. Furthermore, our data suggest that both Tau and BubR1 may be a promising prognostic marker rather than predictive marker in patients with prostate cancer.

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