FGFR3 overexpression is prognostic of adverse outcome for muscle-invasive bladder carcinoma treated with adjuvant chemotherapy
FGFR3 overexpression is prognostic of adverse outcome for muscle-invasive bladder carcinoma treated with adjuvant chemotherapy
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DOI：
10.1016/j.urolonc.2013.07.015
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发表时间：
2014-01-01
影响因子：
2.7
通讯作者：
Kwon, Ghee Young
中科院分区：
文献类型：
--
作者：
Sung, Ji-Youn;Sun, Jong-Mu;Kwon, Ghee Young
背景：成纤维细胞生长因子受体3（FGFR 3）的改变与尿路上皮癌的发病机制有关。然而，其临床病理意义尚未明确，特别是在肌肉浸润性膀胱癌（MIBC）。目的：本研究的目的是探讨FGFR 3基因突变和过表达在胃癌根治性转移中的作用，并分析其在胃癌根治性转移中辅助化疗与非辅助化疗的预后及预测意义。研究FGFR 3外显子7、10和15的突变状态，并评价蛋白表达。结果：7例（9.7%）患者FGFR 3基因突变与乳头状生长、中度组织学分级（62 vs. 13）和中晚期TNM分期（II III vs. IV）相关。33例（45.8%）FGFR 3蛋白过表达，但与相关临床病理参数无关。接受辅助化疗的患者。FGFR 3过表达与较短的无病生存期（P = 0.067，95%置信区间：14.8-29.6，边缘显著性）和总生存期（P = 0.035）相关，在使用考克斯比例风险模型的多变量分析中，FGFR 3过表达仍然是无病生存期和总生存期的显著独立预后因素。未接受辅助化疗的患者。FGFR 3突变或过表达在多因素分析中没有预后意义。结论：我们报告了MIBCs中FGFR 3的改变，并讨论了其在患者亚群中的生物学意义。FGFR 3过表达可预测根治性膀胱癌术后辅助顺铂化疗患者的不良结局。建议将FGFR 3作为治疗靶点。(C)2014 Elsevier Inc. All rights reserved.
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 (62 vs. (13), and moderately advanced TNM stage (II Ill vs. IV). FGFR3 protein overexpression was detected in 33 cases (45.8%) hut 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. (C) 2014 Elsevier Inc. All rights reserved.