title: Abnormal expression of multiple proteins predicts cancer-specific mortality in patients with high-grade non-muscle-invasive bladder cancer treated with transurethral resection.
abstract: High-grade non-muscle-invasive bladder urothelial carcinoma leads to various outcomes. It can cause death even after radical cystectomy and is treated only by transurethral resection (TUR). In the present study, we aimed to determine whether the molecular markers E-cadherin, coxsackie adenovirus receptor (CAR), S100A4 and uroplakin III are associated with clinicopathological outcomes in patients with high-grade non-muscle invasive bladder cancer (NMIBC) treated with TUR. Immunohistochemical staining was performed on serial sections from specimens obtained from 77 patients. Expression patterns were stratified according to the number of abnormally expressed markers: 0-1 or ≥2. The median follow-up time was 56 months (range, 3-287). The results from the present study indicated that expression of E-cadherin, CAR, S100A4 and uroplakin III was abnormal in 16, 17, 27 and 61% of tumors, respectively. Results of the log-rank test revealed that patients with abnormal expression of multiple molecular markers had a significantly increased risk of bladder cancer-specific mortality (P=0.016). The 5-year cancer-specific survival rates were 91 and 66% for patients with 0-1 and ≥2 molecular markers, respectively. No individual marker was associated with disease prognosis. Multivariate models that included clinicopathological outcomes and classified molecular markers indicated that abnormal expression of multiple molecular markers and lack of bacillus Calmette-Guérin (BCG) instillation are predictors of cancer-specific death (P=0.046 and 0.029, respectively). Abnormal expression of multiple molecular markers is a strong predictor of mortality in bladder cancer patients undergoing TUR, suggesting that high-grade non-muscle-invasive cancer is characterized by a variety of pathophysiological pathways. A combination of molecular markers may be useful in a minimally invasive modality for determining prognosis.
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan ;
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Tsumura
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan ;
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan ;
authors.forename: Masaomi
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan ;
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan ;
authors.forename: Takefumi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan ;
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Iwamura
keywords: bladder cancer; high-grade; immunohistochemistry; non-muscle-invasive bladder cancer; survival