TY  - JOUR
A1  - Koll, Florestan J.
A1  - Schwarz, Alina
A1  - Köllermann, Jens
A1  - Banek, Séverine
A1  - Kluth, Luis
A1  - Wittler, Clarissa
A1  - Bankov, Katrin
A1  - Döring, Claudia
A1  - Becker, Nina
A1  - Chun, Felix
A1  - Wild, Peter Johannes
A1  - Reis, Henning
T1  - CK5/6 and GATA3 defined phenotypes of muscle-invasive bladder cancer: impact in adjuvant chemotherapy and molecular subtyping of negative cases
T2  - Frontiers in medicine
N2  - 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.
KW  - bladder cancer
KW  - molecular subtyping
KW  - immunohistochemistry
KW  - adjuvant chemotherapy
KW  - double negative
KW  - consensus classification
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/71664
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-716648
SN  - 2296-858X
N1  - The names of the repository/repositories and accession number(s) can be found below: The gene expression omnibus (GEO) with accession GSE198607 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE198607).
VL  - 9
IS  - art. 875142
PB  - Frontiers Media
CY  - Lausanne
ER  -