Molecular subtype classification of urothelial carcinoma in Lynch syndrome

We aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer. 41 tumor samples from the urinary bladder, or upper urinary tract were included. RNA was isolated from macro-dissected FFPE blocks. Gene expression data was normalized, centered and summarized at the gene level. Hierarchical clustering indicates three clusters of Urothelial Lynch syndrome tumors. Molecular subtype classification was performed by a casewise nearest-neighbor (Pearson-r) comparison to a large published dataset on sporadic urothelial bladder cancer generated by the same method and platform as here.