Molecular profile of micropapillary urothelial carcinoma of the urinary bladder: An analysis of 99 cases by next-generation sequencing.

Micropapillary urothelial carcinoma (MPUC) is an aggressive neoplasm with distinct histology. We examined the molecular profile of MPUC and its relationship to patients' clinicopathologic features in 99 patients who underwent next-generation sequencing from 2010 to 2020 at a single institution. The patients included 77 men and 22 women with a mean age of 68 years (range, 24-91 years). Next-generation sequencing was performed on primary (n = 74) and metastatic (n = 25) tumor specimens. Somatic gene mutations were detected in 98 tumors, and the most common mutations were TP53 (n = 71), TERT (n = 49), ARID1A (n = 28), ERBB2 (n = 24), and RB1 (n = 22). Copy number variations were detected in 22 tumors, including ERBB2 (n = 8), CDK12 (n = 3), CCND1 (n = 3), and other genes (n = 8). No gene fusions or microsatellite instability was detected. Human epidermal growth factor receptor 2 (HER2) overexpression was detected more frequently in MPUCs with ERBB2 amplifications than those with ERBB2 mutations. Individual gene mutations did not significantly affect the overall survival, but patients with ERBB2 amplifications had a significantly shorter overall survival than those with ERBB2 mutations (p = 0.043). MPUC demonstrated distinct gene alterations in oncogenes and tumor suppressor genes that may be involved in MPUC's oncogenesis. ERBB2 gene amplifications were associated with HER2 overexpression in MPUC, which may contribute to MPUC's aggressive behavior.