Potential for molecular-targeted therapy targeting human epidermal growth factor receptor-2 for invasive bladder cancer

Abstract

Expression of human epidermal growth factor receptor-2 (HER-2/neu or HER-2) oncoprotein in invasive bladder cancer was examined by immunohistochemical staining in order to evaluate the potential for molecular-targeted therapy targeting HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients who were examined at Aichi Medical University Hospital and were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2 to pT4). Immunohistochemical staining using a Hercep test kit was performed to detect HER-2 expression, which was classified into four levels from 0 to 3+ by two experienced pathologists, with 2+ and 3+ determined as positive. HER-2 staining in the primary tumor was determined as 0 in 9 (22.5%) patients, 1+ in 14 (35%), 2+ in 10 (25%), and 3+ in 7 (17.5%), resulting in 17 (17/40, 42.5%) HER-2-positive patients. According to the classification of grade, one (1/3, 33.3%) grade 2 patient and 16 (16/37, 43.2%) grade 3 patients were HER-2 positive (p=0.99). According to the classification of stage, 12 (12/22, 54.5%) pT2 patients, 2 (2/13, 15.3%) pT3 patients, and 3 (3/5, 60%) pT4 patients were HER-2 positive (p=0.05). Lymph node metastasis was found in 10 patients, and 3 (3/6, 50%) pN2 patients were HER-2 positive (p=0.32). There was a statistically significant difference between patients with HER-2-positive primary tumors and those with HER-2-positive metastatic lymph nodes (p=0.02). This study suggested that 42.5% of patients with invasive bladder cancer may benefit from molecular-targeted therapy targeting HER-2, and that the efficacy of molecular-targeted therapy can be expected even for patients with lymph node metastases as long as their primary tumors are HER-2 positive.