CK5/6 and GATA3 defined phenotypes of muscle-invasive bladder cancer: impact in adjuvant chemotherapy and molecular subtyping of negative cases

  • 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 < 0.001) and double-negative cases had decreased OS (HR: 4.07; 95% CI: 1.5–10.9, p = 0.005). Double negative cases were classified as NE-like (30%), stroma-rich (30%), and Ba/Sq (40%) consensus molecular subtypes and displaying different histological subtypes.

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Author:Florestan J. KollORCiD, Alina SchwarzGND, Jens KöllermannORCiDGND, Séverine BanekGND, Luis KluthORCiDGND, Clarissa Wittler, Katrin BankovORCiDGND, Claudia DöringGND, Nina Becker, Felix ChunORCiDGND, Peter Johannes WildORCiDGND, Henning ReisORCiDGND
Parent Title (English):Frontiers in medicine
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Date of Publication (online):2022/06/16
Date of first Publication:2022/06/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/01/24
Tag:adjuvant chemotherapy; bladder cancer; consensus classification; double negative; immunohistochemistry; molecular subtyping
Issue:art. 875142
Article Number:875142
Page Number:9
The names of the repository/repositories and accession number(s) can be found below: The gene expression omnibus (GEO) with accession GSE198607 (
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International