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

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, BRCA1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin α3β1 (AG) and CK5/6) were developed. BC samples from patients who showed a pathologic response ( n =?39) and non-response ( n =?13) were applied to the panel analysis. ERBB2 , FGFR3 and PIK3CA 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.