Frequency and clinicopathologic correlates of ErbB1, ErbB2, and ErbB3 immunoreactivity in urothelial tumors of upper urinary tract

Abstract

ObjectivesTo investigate the frequency and clinicopathologic correlates of ErbB1, ErbB2, and ErbB3 receptor expression in patients with upper urothelial carcinoma. MethodsImmunohistochemical staining for ErbB1, ErbB2, and ErbB3 was done with serial sections from archival specimens of 94 patients who underwent nephroureterectomy plus bladder cuff resection for urothelial carcinoma of the renal pelvis and ureter (median follow-up 40 months, range 1 to 177). The correlates between ErbB receptor expression and clinical outcome in terms of recurrence, progression, disease-free survival, and overall survival were analyzed by Kaplan-Meier plots, with the log-rank test and Cox proportional hazards model. ResultsErbB1, ErbB2, and ErbB3 expression was present in 9 (9.5%), 13 (13.8%), and 26 (27.7%) tumors, respectively. Thirty-seven patients (39.4 %) had at least one receptor expressed and eight (8.5%) had coexpression of two or three receptors. ErbB2 expression was significantly associated with tumor invasiveness (P = 0.03), and ErbB1 and ErbB3 expression was not. The incidence of subsequent tumor recurrence in the urinary bladder correlated significantly with ureteral tumor involvement and ErbB2 expression (P = 0.04 and P = 0.04, respectively). On univariate and multivariate analyses, tumor staging and ErbB2 expression were independent predictors of disease progression (P = 0.01 and P = 0.01, respectively), disease-free survival (P = 0.02 and P = 0.002, respectively), and overall survival (P = 0.01 and P = 0.02, respectively). ConclusionsErbB2 expression predicts for disease progression and disease-related survival in upper urothelial carcinoma.