Low Grade Bladder Tumors Progress to High Grade via Two Distinct Mechanisms
Sources of Funding: None
Introduction
Low-grade (LG) urothelial carcinoma of the bladder (UCB) are common malignancies that are costly to surveil and infrequently progress to life threatening, high-grade (HG) malignancies. It is not clear whether the progression of LG to HG is a result of second primaries or transformation of LG tumors. We sought to examine tumor genetics in patients who progressed from LG to HG urothelial carcinoma and compared to patients with no progression.
Methods
An institutional cancer database at a tertiary referral center in the United States was queried for living patients who progressed from LG to HG UCB. Histologic re-review was performed by a genitourinary pathologist. Whole exome sequencing with correction for germline mutations by buffy coat subtraction was performed. Mutations were assessed for continuity or novelty between low grade tumors and subsequent same-patient HG tumors and for LG patients who did not progress. Individual genes were assessed for potential predictors of risk for progression.
Results
Five patients were identified with progression. Clinicopathologic variables were identified and median time to progression from initial low-grade diagnosis was 19 months. Both true tumor progression and de novo growth of high grade tumors were identified. Gene alterations associated with tumor grade progression in initial low grade tumors were FBN3, CIT and HECTD4.
Conclusions
Both true tumor progression and de novo high-grade tumors were observed in initial low grade urothelial carcinomas that progressed. Validation of the identified tumor genes that appeared associated with progression may provide a clinically valuable tool to providers managing patients with low grade urothelial carcinomas.
Funding
None
Christine Shiang
Ryan Hutchinson
Rahul Kollipara
Payal Kapur
Franto Francis
Yair Lotan