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CK5/6 and GATA3 Defined Phenotypes of Muscle-invasive Bladder Cancer: Impact in Adjuvant Chemotherapy and Molecular Subtyping of Negative Cases

Florestan J. KollAlina SchwarzJens KöllermannSéverine BanekLuis Alex KluthClarissa WittlerKatrin BankovClaudia DöringNina BeckerFelix ChunPeter Johannes WildHenning Reis

出版	Frontiers Media, 2022
URL	http://books.google.com.hk/books?id=JYnazwEACAAJ&hl=&source=gbs_api

註釋Introduction and Objective: Identifying patients that benefit from cisplatin-based adjuvant chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC). The purpose of this study is to correlate "luminal" and "basal" type protein expression with histological subtypes, to investigate the prognostic impact on survival after adjuvant chemotherapy and to define molecular consensus subtypes of "double negative" patients (i.e., without expression of CK5/6 or GATA3). Materials and Methods: We performed immunohistochemical (IHC) analysis of CK5/6 and GATA3 for surrogate molecular subtyping in 181 MIBC samples. The mRNA expression profiles for molecular consensus classification were determined in CK5/6 and GATA3 (double) negative cases using a transcriptome panel with 19.398 mRNA targets (HTG Molecular Diagnostics). Data of 110 patients undergoing radical cystectomy were available for survival analysis. Results: The expression of CK5/6 correlated with squamous histological subtype (96%) and expression of GATA3 was associated with micropapillary histology (100%). In the multivariate Cox-regression model, patients receiving adjuvant chemotherapy had a significant survival benefit (hazard ratio [HR]: 0.19 95% confidence interval [CI]: 0.1-0.4, p