Mp38-09 Prognostic Significance of Ron and Her2 Receptors in Upper Tract Urothelial Carcinoma

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II (MP38)1 May 2024MP38-09 PROGNOSTIC SIGNIFICANCE OF RON AND HER2 RECEPTORS IN UPPER TRACT UROTHELIAL CARCINOMA Hsiu-Ting Tung, Yeong-Chin Jou, Hsin-Tzu Tsai, Tzong-Shin Tzai, Lin-Nei Hsu, Nan-Hua Chow, and Yuh-Shyan Tsai Hsiu-Ting TungHsiu-Ting Tung , Yeong-Chin JouYeong-Chin Jou , Hsin-Tzu TsaiHsin-Tzu Tsai , Tzong-Shin TzaiTzong-Shin Tzai , Lin-Nei HsuLin-Nei Hsu , Nan-Hua ChowNan-Hua Chow , and Yuh-Shyan TsaiYuh-Shyan Tsai View All Author Informationhttps://doi.org/10.1097/01.JU.0001008700.92603.b1.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The recepteur d'origine Nantais (RON) and the human epidermal growth factor receptor (HER) family are important receptor tyrosine kinases (RTKs) with diverse biological functions. Aberrant activation of RON and HER family receptors had been reported in epithelial carcinogenesis across various type of cancers. Our prior study revealed the existence of cross-talk between EGFR and RON during urothelial carcinogenesis of the human urinary bladder, and co-expression of both receptors was associated with poorer survival outcomes. However, the clinical significance of RON and HER family receptors in patients with upper tract urothelial carcinoma (UTUC) remains unexplored. This study aims to investigate the prognostic value of RON and HER family receptor expression status in UTUC patients. METHODS: Immunohistochemical staining for RON, EGFR, HER2, and HER3 was performed on serial sections of archival tissue specimens from 124 patients with UTUC who underwent nephroureterectomy plus bladder cuff resection. Clinicopathological characteristics were retrospectively reviewed, and survival status was determined by medical records. The associations between clinicopathological variables, expression status of receptors and disease-specific survival were analyzed. The study protocol was approved by the institutional review board of National Cheng Kung University Hospital (Registry number: A-ER-103-012 and A-ER-103-036). RESULTS: With a median follow-up duration of 50 months (range 1-177 months), 41 UTUC-related deaths were recorded. RON, EGFR, HER2, and HER3 expression was positive in 45 of 124 (36.3%), 20 of 124 (16.1%), 13 of 96 (13.5%), and 26 of 96 (27.1%) tumors, respectively. Among 45 RON-positive tumors, 8 (17.8%), 5 (15.2%), and 6 (18.2%) had EGFR, HER2, and HER3 co-expression, respectively. HER2 expression was significantly associated with an increased risk of distant metastasis (OR 7.64, p<0.001). Univariate Cox regression analyses showed that stage, grade, RON expression, and metastasis were associated with poorer disease-specific survival, and multivariate analyses revealed that RON (HR 2.15, p=0.017) and metastasis (HR 4.37, p<0.001) remained as significant predictors of poor survival. Co-expression of RON and HER2 was associated with the worst survival (Logrank p=0.0048). CONCLUSIONS: RON expression was found in one-third of UTUC and was an independent predictor of poor disease-specific survival. UTUC with RON/HER2 co-expression had the most aggressive behavior and the worst outcome. Source of Funding: This research was supported by the National Cheng Kung University Hospital of Taiwan and the Ministry of Science and Technology of Taiwan © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e644 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Hsiu-Ting Tung More articles by this author Yeong-Chin Jou More articles by this author Hsin-Tzu Tsai More articles by this author Tzong-Shin Tzai More articles by this author Lin-Nei Hsu More articles by this author Nan-Hua Chow More articles by this author Yuh-Shyan Tsai More articles by this author Expand All Advertisement PDF downloadLoading ...