HER2 Status in Molecular Subtypes of Urothelial Carcinoma of the Renal Pelvis and Ureter.

Abstract

Erb-b2 receptor tyrosine kinase 2 (ERBB2, also known as HER2) gene amplification or protein overexpression occurs in certain types of urothelial carcinomas. Molecular pathologic classification of urinary bladder cancer using immunohistochemistry has identified basal and luminal subtypes with differing prognoses, but the HER2 status of these subtypes has not been investigated. In addition, research on urothelial carcinoma of the renal pelvis and ureter (UCRPU) has not progressed because of its rarity, though its prognosis is worse than that of bladder cancer. In this study, we evaluated the clinical significance of HER2 status in molecular subtypes of UCRPU. HER2 status (protein overexpression and/or gene amplification) and molecular subtyping were determined for 148 cases of UCRPU (83 and 65 cases in the renal pelvis and ureter, respectively), using immunohistochemistry and fluorescent in situ hybridization, and compared with clinicopathologic factors. Subtype analysis revealed that the cases were 46% basal and 54% luminal. HER2 protein overexpression and/or gene amplification was observed in 14% of UCRPU cases and was significantly more frequent in the luminal subtype than in the basal (22% vs. 4%; P= .0030). Univariate analysis showed that the overall survival of patients with HER2-positive UCRPU was significantly shorter than those with HER2-negative tumors. HER2 protein overexpression and gene amplification were specifically observed in the luminal subtype of UCRPU, suggesting that these cases may respond to HER2-targeted therapies like trastuzumab.