You have accessJournal of UrologyOutstanding Posters: Research1 Apr 2014OP1-12 REDUCED TRAP1 EXPRESSION IS ASSOCIATED WITH POOR PROGNOSIS IN UPPER URINARY TRACT UROTHELIAL CARCINOMA PATIENTS: ITS IMPLICATIONS FOR TUMOR INVASION Hiroshi Fukushima, Soichiro Yoshida, Fumitaka Koga, Yasukazu Nakanishi, Toshiki Kijima, Junichiro Ishioka, Yoh Matsuoka, Noboru Numao, Kazutaka Saito, Yasuhisa Fujii, and Kazunori Kihara Hiroshi FukushimaHiroshi Fukushima More articles by this author , Soichiro YoshidaSoichiro Yoshida More articles by this author , Fumitaka KogaFumitaka Koga More articles by this author , Yasukazu NakanishiYasukazu Nakanishi More articles by this author , Toshiki KijimaToshiki Kijima More articles by this author , Junichiro IshiokaJunichiro Ishioka More articles by this author , Yoh MatsuokaYoh Matsuoka More articles by this author , Noboru NumaoNoboru Numao More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Yasuhisa FujiiYasuhisa Fujii More articles by this author , and Kazunori KiharaKazunori Kihara More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.620AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a molecular chaperone abundantly expressed in mitochondria. TRAP1 negatively regulates oxidative phosphorylation by regulating the activity of the mitochondrial respiratory chain. TRAP1 also functions as an invasion-suppressor by modulating reactive oxygen species (ROS) in some cancer cell lines. Here, we investigated the functional and prognostic role of TRAP1 in upper tract urothelial carcinoma (UTUC). METHODS To investigate the role of TRAP1 in UC invasion, a loss-of-function and a gain-of-function approach were applied to a human UC cell line (5637 cells). Cell invasion was evaluated with a Matrigel Invasion Assay. Furthermore, TRAP1 expression was evaluated immunohistochemically in tumor specimens obtained from 62 UTUC patients (cTa-4N0M0) treated with radical nephroureterectomy alone. TRAP1 expression was visually scored on a scale of 0 to 3+. We analyzed the association of TRAP1 expression as well as clinicopathological factors including age, gender, pathological T stage, grade and lymph node involvement with cancer-specific survival (CSS). RESULTS We identified endogenous TRAP1 protein in mitochondrial preparations only. Transient TRAP1 knockdown enhanced cell invasion. This increased cell invasion was attenuated by ROS scavenging agent N-acetylcysteine, suggesting that ROS may contribute to enhanced cell invasion introduced through TRAP1 silencing. TRAP1-Flag overexpression hampered cell invasion . The impact of TRAP1 expression on cell invasion suggested an association between aggressiveness of UTUC and reduced TRAP1 expression. Of the total 62 patients, 33 (53%) showed low TRAP1 expression (0 and 1+). During a median follow-up of 60 months, 16 (48%) of 33 with lower TRAP1 expression (0 and 1+) and two (7%) of 29 with higher TRAP1 expression (2+ and 3+) died of cancer (5-y CSS of 52% vs. 95%; p < 0.001). On multivariate analysis, lower TRAP1 expression was an independent predictor of shorter CSS (HR 21.85, p < 0.001), along with grade (p < 0.001) and lymph node involvement (p = 0.014). CONCLUSIONS Reduced TRAP1 expression is associated with increased invasive potential via ROS modulation and poor prognosis in UTUC. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e166-e167 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Hiroshi Fukushima More articles by this author Soichiro Yoshida More articles by this author Fumitaka Koga More articles by this author Yasukazu Nakanishi More articles by this author Toshiki Kijima More articles by this author Junichiro Ishioka More articles by this author Yoh Matsuoka More articles by this author Noboru Numao More articles by this author Kazutaka Saito More articles by this author Yasuhisa Fujii More articles by this author Kazunori Kihara More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...