Ji-Youn Sung1, Jong-Mu Sun2, Byong Chang Jeong3, Seong Il Seo3, Seong Soo Jeon3, Hyun Moo Lee3, Han Yong Choi3, So Young Kang4, Yoon-La Choi5, Ghee Young Kwon6. 1. Department of Pathology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea. 2. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 3. Department of Urology, Samsung Medical center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 4. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 5. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: geeo@skku.edu. 6. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: ylachoi@skku.edu.
Abstract
BACKGROUND: Alterations in fibroblast growth factor receptor 3 (FGFR3) have been implicated in the pathogenesis of urothelial carcinoma. However, its clinicopathological significance has not been clearly established, especially in muscle-invasive bladder cancer (MIBC). OBJECTIVES: The aim of our study was to investigate the mutation and overexpression of FGFR3 in MIBC cases from radical cystectomy and to analyze the prognostic and predictive significance in the groups with or without adjuvant chemotherapy. METHODS AND MATERIALS: Study cohorts included 72 cases of MIBC including 42 patients who were treated with adjuvant chemotherapy. The mutation status of FGFR3 exons 7, 10, and 15 was investigated and protein expression was evaluated. The findings were analyzed for the association with relevant clinicopathological findings. RESULTS: FGFR3 mutations were found in 7 patients (9.7%) and were correlated with a pattern of papillary growth, moderate histologic grade (G2 vs. G3), and moderately advanced TNM stage (II-III vs. IV). FGFR3 protein overexpression was detected in 33 cases (45.8%) but was not associated with the relevant clinicopathological parameters. In patients treated with adjuvant chemotherapy, FGFR3 overexpression was correlated with shorter disease-free survival (P = 0.067, 95% confidence interval: 14.8-29.6, marginal significance) and overall survival (P = 0.035), remaining as a significant independent prognostic factor for disease-free survival and overall survival in multivariate analysis using Cox proportional hazards model. In patients without adjuvant chemotherapy, FGFR3 mutation or overexpression did not have prognostic significance in multivariate analysis. CONCLUSION: We report the FGFR3 alterations in MIBCs, and discuss their biological implication in subsets of patients. FGFR3 overexpression was predictive of adverse outcome in patients with adjuvant cisplatin-based chemotherapy after radical cystectomy. The utility of FGFR3 as a therapeutic target is suggested.
BACKGROUND: Alterations in fibroblast growth factor receptor 3 (FGFR3) have been implicated in the pathogenesis of urothelial carcinoma. However, its clinicopathological significance has not been clearly established, especially in muscle-invasive bladder cancer (MIBC). OBJECTIVES: The aim of our study was to investigate the mutation and overexpression of FGFR3 in MIBC cases from radical cystectomy and to analyze the prognostic and predictive significance in the groups with or without adjuvant chemotherapy. METHODS AND MATERIALS: Study cohorts included 72 cases of MIBC including 42 patients who were treated with adjuvant chemotherapy. The mutation status of FGFR3 exons 7, 10, and 15 was investigated and protein expression was evaluated. The findings were analyzed for the association with relevant clinicopathological findings. RESULTS:FGFR3 mutations were found in 7 patients (9.7%) and were correlated with a pattern of papillary growth, moderate histologic grade (G2 vs. G3), and moderately advanced TNM stage (II-III vs. IV). FGFR3 protein overexpression was detected in 33 cases (45.8%) but was not associated with the relevant clinicopathological parameters. In patients treated with adjuvant chemotherapy, FGFR3 overexpression was correlated with shorter disease-free survival (P = 0.067, 95% confidence interval: 14.8-29.6, marginal significance) and overall survival (P = 0.035), remaining as a significant independent prognostic factor for disease-free survival and overall survival in multivariate analysis using Cox proportional hazards model. In patients without adjuvant chemotherapy, FGFR3 mutation or overexpression did not have prognostic significance in multivariate analysis. CONCLUSION: We report the FGFR3 alterations in MIBCs, and discuss their biological implication in subsets of patients. FGFR3 overexpression was predictive of adverse outcome in patients with adjuvant cisplatin-based chemotherapy after radical cystectomy. The utility of FGFR3 as a therapeutic target is suggested.
Authors: David P Perrault; Gene K Lee; Sun Young Park; Sunju Lee; Dongwon Choi; Eunson Jung; Young Jin Seong; Eun Kyung Park; Cynthia Sung; Roy Yu; Antoun Bouz; Austin Pourmoussa; Soo Jung Kim; Young-Kwon Hong; Alex K Wong Journal: Lymphat Res Biol Date: 2019-01-16 Impact factor: 2.589
Authors: Min Yuen Teo; Jose Mauricio Mota; Karissa A Whiting; Han A Li; Samuel A Funt; Chung-Han Lee; David B Solit; Hikmat Al-Ahmadie; Matthew I Milowsky; Arjun V Balar; Eugene Pietzak; Guido Dalbagni; Bernard H Bochner; Irina Ostrovnaya; Dean F Bajorin; Jonathan E Rosenberg; Gopa Iyer Journal: Eur Urol Date: 2020-08-01 Impact factor: 20.096
Authors: Sung Han Kim; Ho Kyung Seo; Hee Chul Shin; Sung Ja Chang; Sooin Yun; Jungnam Joo; Ja Hyeon Ku; Hyung Suk Kim; Hwang Gyun Jeon; Byong Chang Jeong; In Gab Jeong; Seok Ho Kang; Bumsik Hong Journal: J Korean Med Sci Date: 2015-07-15 Impact factor: 2.153