HER2 overexpression in muscle‐invasive urothelial carcinoma of the bladder: Prognostic implications

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Abstract
The HER2 (c‐erbB‐2) receptor is overexpressed in a variety of human malignant tumors and, in breast carcinoma, has been identified as a target for anti‐HER2–directed therapy with the monoclonal antibody (MAb) trastuzumab. The aim of this retrospective study was to evaluate immunohistochemic HER2 expression in a large cohort of muscle‐invasive urothelial cell carcinomas of the urinary bladder and to compare the results to pathologic characteristics and survival. Paraffin‐embedded tumor specimens from 138 patients undergoing radical cystectomy for muscle‐invasive bladder carcinoma were studied immunohistochemically with the Food and Drug Administration (FDA)‐approved HercepTest (Dako, Glostrup, Denmark). HER2 overexpression was observed in 57 of 138 tumors (41%) and occurred more frequently in high‐grade carcinomas than in low‐grade carcinomas (p = 0.036). No significant relationship with HER2 overexpression was registered for tumor staging and lymph node status. Kaplan‐Meier curves showed a significantly worse disease‐related survival (p = 0.034) in patients with HER2‐overexpressing tumors compared to those without HER2 overexpression. In addition to lymph node status (p = 0.0001; relative risk [RR] = 2.93), HER2 status (p = 0.020; RR = 2.22) was identified as an independent predictor for disease‐related survival in a multivariate analysis. These results suggest that HER2 expression might provide additional prognostic information in patients with muscle‐invasive bladder carcinomas. Because many of these patients harbor HER2‐overexpressing tumors, clinical trials evaluating the efficacy of trastuzumab in bladder carcinoma are warranted.