IBCN 2018: Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer
A comprehensive genomic analysis was performed on 28 cases of SARCs and 84 cases of conventional UCs, with the TCGA cohort of 408 muscle-invasive bladder cancers serving as the reference cohort. SARCs showed a distinct mutational landscape with enrichment of TP53, RB1, and PIK3CAmutations. They were related to the basal molecular subtype of conventional UCs and could be divided into “epithelial” and more clinically aggressive “mesenchymal” subsets. Expression analysis showed that SARCs are driven by downregulation of TP63 and dysregulation of cell cycle and EMT regulatory networks, and nearly half exhibited a heavily infiltrated immune phenotype with PD-L1 upregulation.
In summary, they found SARCs were driven by profound dysregulation of the EMT network and that a large proportion of SARCs has an immune infiltration phenotype. Both these features present new avenues of therapeutic potential in patients with this highly lethal variant of bladder cancer.
Presented by: Bogdan Czerniak, MD, The University of Texas MD Anderson Cancer Center, Houston, TX
Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands