HER2/neu expression in bladder cancer: relationship to cell cycle kinetics

BACKGROUND AND OBJECTIVES: The incidence of overexpression of HER2/neu in bladder cancer is one of the highest among all human malignancies tested; such overexpression is thought to play a role in the aberrant proliferation of cancer cells. This study was conducted to evaluate the quantitative assessment of HER2/neu expression by enzyme immunoassay (EIA) and its prognostic significance in differentiating between high and low proliferating tumors. PATIENTS AND METHODS: Tissue samples were collected from 35 patients with benign bladder lesions, 28 with bilharzial bladder cancer, and 25 with nonbilharzial bladder cancer. Twenty normal samples were obtained from normal safety margin areas in nonbilharzial bladder cancer patients. Out of the malignant samples, 22 were found to be squamous cell carcinoma and 31 were transitional cell carcinoma. All samples were examined for HER2/neu expression by EIA and Western blot (WB). Flow cytometric (FCM) analysis was also performed in all the samples provided. RESULTS: HER2/neu was found to be significantly overexpressed in the malignant group compared to the benign and normal groups (P < 0.001) and no significant difference was found between the bilharzial and nonbilharzial cancer groups or between the transitional and squamous cell carcinoma groups. HER2/neu was significantly correlated to ploidy (P = 0.001), synthetic phase fraction, SPF (P = 0.012), and DNA index (P = 0.002). No significant correlation was found between HER2/neu and stage or grade while it was significantly associated with lymph node status of the tumour (P = 0.02). CONCLUSION: HER2/neu can be measured reliably by the EIA method as confirmed by WB. The quantitative assessment of HER2/neu expression in malignant tumors aided by other proliferation markers such as SPF, DI, and ploidy could be useful in selecting patients for more aggressive treatment or for predicting outcome.