Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers with Response to Neoadjuvant Chemotherapy

文献类型： 外文期刊

第一作者： Yang, Zhao

作者： Yang, Zhao;Kang, Xing;Zhang, Xu;Quan, Xiaofang;Li, Chong;Yang, Zhao;Zhang, Ruiyun;Chen, Haige;Ge, Yunxia;Wang, Yue;Song, Chengli;Qin, Xuying;Wang, Haifeng;Li, Chong;Li, Chong

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关键词： Bladder cancer; Neoadjuvant chemotherapy; FGFR3; ERCC1

期刊名称：EBIOMEDICINE （ 影响因子：8.143； 五年影响因子：8.333 ）

ISSN： 2352-3964

年卷期： 2018 年 35 卷

页码：

收录情况： SCI

摘要： The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy benefits overall survival for patients with muscle-invasive bladder cancer (MIBC). However, the relationship between the genetic profiling of MIBC and NAC response remains unclear. Here, a mutation panel of six cancer-associated genes (TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC) panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA 1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin alpha 3 beta 1 (AG) and CK5/6) were developed. BC samples from patients who showed a pathologic response (n = 39) and nonresponse (n = 13) were applied to the panel analysis. ERBB2, FGFR3 and RICCA exclusively altered in the responders group (19/39,48.7%), in which FGFR3 mutations were significantly enriched in patients with a response in the cohort (14/39, 35.9%; P = 0.01). Additionally, strong expression of ERCC1 was associated with a pathologic response (P = 0.01). However, positive lymph node metastasis (P < 0.01) and lymph-vascular invasion (LVI) (P = 0.03) were correlated with a non-response. Overall, the data show that FGFR3 mutations and elevated expression of ERCC1 in MIBCs are potential predictive biomarkers of the response to NAC. (C) 2018 Published by Elsevier B.V.

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