Prostate tumor overexpressed 1 expression in invasive urothelial carcinoma.

PURPOSE: To determine the expression patterns of the proliferation marker prostate tumor overexpressed 1 (PTOV1) in invasive urothelial cancer (UC). METHODS: Corresponding UC and benign samples from paraffin-embedded tissue of 102 patients treated with cystectomy for invasive UC were immunohistochemically (IHC) assessed for PTOV1. Expression was evaluated gradually separated for cytoplasmic and nuclear staining. Results were correlated to histological and clinical data. To correlate PTOV1 expression with molecular subtypes of UC, analysis of PTOV1 RNA expression data of the Cancer Genome Atlas UC cohort was performed. RESULTS: PTOV1 expression was present in UC and benign urothelium, whereby nuclear staining was significantly more frequent in UC tissue (p = 0.0004). Lower cytoplasmic expression was significantly associated with pathological stage >pT2 (p = 0.0014) and grade ≥G3 (p = 0.0041), respectively. IHC expression patterns did not show correlation to survival data. PTOV1 RNA expression correlated with features of the luminal UC subtype. CONCLUSIONS: Subcellular distribution seems to be the most important feature of PTOV1 expression in UC. Nuclear localization of PTOV1 along with cytoplasmic decrease in PTOV1 expression was identified as putative surrogate for PTOV1-associated cellular proliferation and dedifferentiation in UC. The functional relevance as well as the potential role of PTOV1 as a biomarker in UC remains to be specified in future studies.

Muscle-invasive bladder cancer is characterized by overexpression of thymidine kinase 1.

OBJECTIVE: Thymidine kinases have an important role in the synthesis of DNA and exhibit high activity in rapidly proliferating cells. Thymidine kinase 1 (TK1) activity has been shown to be increased in various cancer types and proposed as a prognostic parameter. Aim of the present study was to investigate TK1 in muscle-invasive urothelial carcinoma (UC). METHODS: Corresponding UC and benign samples from paraffin embedded tissue of 111 patients treated with cystectomy for invasive UC from 1996 to 2006 were immunohistochemically (IHC) assessed for TK1. IHC expression patterns were evaluated in a semiquantitative fashion by 2 independent reviewers. Localization of staining was categorized into pure nuclear and additional cytoplasmic localization. Uni- and multivariate analyses were performed to assess differential expression in normal and UC tissue and to evaluate the diagnostic and predictive capability of TK1 by correlation to clinical data. To correlate TK1 expression with molecular subtypes of UC, analysis of TK1 RNA expression levels of the Cancer Genome Atlas UC cohort was performed. RESULTS: TK1 was significantly overexpressed in invasive UC, compared to benign urothelium (P<0.0001), and cytoplasmic expression was more often found in cancer tissue than in benign tissue (P = 0.0001). No correlations of TK1 protein expression patterns to standard histopathological determinants were detected. In univariate analysis, TK1 nuclear and cytoplasmic expression was associated with improved cancer-specific survival (P = 0.0119). However, only metastasis status and histologic grade were identified as independent predictors of cancer-specific survival in multivariate analysis. TK1 expression was merely found in the basal layers of benign urothelium. RNA overexpression of TK1 could be correlated to the biologically more aggressive basal UC subtype. CONCLUSIONS: TK1 expression is significantly different in invasive UC and benign urothelium, which underlines its potential as a diagnostic marker. Although TK1 is considered to be a marker of proliferation, and TK1 RNA overexpression is associated with an aggressive UC subtype, its capability as a predictive IHC biomarker for invasive UC remains limited.