Introduction: To evaluate the impact of HER2 immunoreactivity on clinical outcome in locally advanced urothelial carcinoma patients who received surgery alone, or methotrexate, vinblastine, epirubicin, and cisplatin (M-VEC) as adjuvant chemotherapy. Materials and Methods: We studied 114 formalin-fixed paraffin-embedded specimens obtained from locally advanced urothelial carcinoma patients receiving surgery alone or adjuvant M-VEC. The authors evaluated HER2 immunoreactivity using immunohistochemical staining and explored the influence of pathological parameters and HER2 immunoreactivity on progression-free survival (PFS) and disease-specific overall survival (OS) using univariate and multivariate Cox’s analyses. Results: Urothelial carcinoma of the bladder had a significantly higher frequency of HER2 immunoreactivity than that of the upper urinary tract (60.7 vs. 20.7%, p < 0.0001). Overall, nodal status was a strong and independent prognostic indicator for clinical outcome. The HER2 immunoreactivity was significantly associated with PFS (p = 0.02) and disease-specific OS (p = 0.005) in advanced urothelial carcinoma patients. As for patients with adjuvant M-VEC, HER2 immunoreactivity was a significant prognostic factor for PFS (p = 0.03) and disease-specific OS (p = 0.02) using univariate analysis, but not multivariate analysis, and not for patients receiving watchful waiting. Conclusions: HER2 immunoreactivity might have a limited prognostic value for advanced urothelial carcinoma patients with adjuvant M-VEC.

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