Expression Analysis of Same-Patient Metachronous and Synchronous Upper-Tract and Bladder Urothelial Carcinoma.

To compare upper-tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) in same-patient metachronous-(m) and synchronous-(s) UTUC and BUC using next generation sequencing.

Consecutive untreated same-patient samples of UTUC and BUC were macrodissected from unstained formalin-fixed, paraffin-embedded slides after quality control. Samples were divided into 4 groups: 1) UTUC-mBUC, 2) BUC-mUTUC, 3) sUTUC-BUC, 4) UTUC without BUC. Exclusions were inadequate clinical data or histological tumor purity <30%. Whole transcriptome RNA sequencing was performed. After quality assessment, gene expression clusters using unsupervised hierarchical consensus clustering (CC) and correlation with pertinent clinicopathologic variables, a prior RNASeq dataset, and other published data were performed.

RNAseq was performed on 95 samples (UTUC=61, BUC=34) from 40 untreated patients. Unsupervised CC segregated the tumors into two clusters that were enriched with BASE47 basal-like or luminal-like gene expression. Almost two-thirds (61.9%) of Group 2 tumors were basal-like, while the majority of Groups 1, 3, 4 (80.6%, 70.0%, and 69.6%, respectively) were luminal-like (p=0.017). Further analyses revealed that the differences in basal-like and luminal-like gene expression were associated with differential fibroblast and immune cell gene expression signatures. 87.5% of metachronous tumors maintained subtype membership.

Gene expression analysis of same-patient metachronous UTUC-BUC suggests that the majority of mUTUC developing after BUC appear more basal-like, while synchronous and initial UTUC tumors appear luminal-like. Metachronous tumors largely maintain molecular subtype membership of the initial tumor regardless of chronologic development or anatomic origin.

The Journal of urology. 2021 Apr 21 [Epub ahead of print]

Firas G Petros, Woonyoung Choi, Yuan Qi, Tyler Moss, Roger Li, Xiaoping Su, Charles C Guo, Bogdan Czerniak, Colin Dinney, David J McConkey, Surena F Matin

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.