Micropapillary urothelial carcinoma exhibits amplification of the human epidermal growth factor receptor, ERBB2(HER2), and overexpression of the ERBB2 protein product.
Mayo clinic researchers, first author John Cheville, M.D., completed a study in Modern Pathology to examine ERBB2 amplification and protein expression in micropapillary urothelial carcinoma and stage-matched typical urothelial carcinoma treated by radical cystectomy to assess the frequency of amplification and protein expression, and to determine the association with cancer-specific survival.
For the study, pathologic material and data from patients undergoing cystectomy at Mayo Clinic between 1980 and 2008 were reviewed. ERBB2 amplification by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry were assessed. Univariate and multivariate Cox proportional hazards regression models were used to evaluate for associations of ERBB2 amplification and protein expression with survival.
According to the results, ERBB2 amplification was identified in 9 (15 percent) of 61 micropapillary carcinomas compared with 9 (9 percent) of 100 urothelial carcinomas. In patients with micropapillary carcinoma, ERBB2 amplification was associated with a nearly threefold increased risk of cancer death. ERBB2 amplification (hazard ratio 4.3; P=0.0008) remained associated with an increased risk of death from bladder cancer among patients with micropapillary urothelial carcinoma on multivariate analysis. However, the association of cancer-specific survival and ERBB2 amplification was not seen in patients with urothelial carcinoma.
While ERBB2 immunohistochemistry correlated with ERBB2 amplification, there was no association of ERBB2 protein expression and survival. Based on the results, ERBB2 amplification is more frequent in micropapillary urothelial carcinoma than typical urothelial carcinoma, and patients with micropapillary carcinoma who have ERBB2 amplification have worse cancer-specific survival than those who do not. Given these findings, identification of ERBB2 amplification in micropapillary carcinoma could provide important prognostic information and possibly provide a role for ERBB2 targeted therapy.
Additional Mayo Clinic authors include: Steven Schneider, William Sukov, M.D., Igor Frank, M.D., Stephen Boorjian, M.D., Brian Costello, M.D., Robert Tarrell, Prabin Thapa, R Houston Thompson, M.D., Matthew Tollefson, M.D., and R Jeffrey Karnes, M.D.