Clinicopathologic significance of the expression of mutated p53 protein and the proliferative activity of cancer cells in patients with esophageal squamous cell carcinoma

Abstract

Background: The aim of this study was to investigate the relation between the expression of mutated p53 protein and the proliferative activity of cancer cells in esophageal squamous cell carcinoma. In addition, the clinical and biologic significance of p53 status and the proliferative activity of cancer cells were evaluated in these patients. Study Design: Samples of esophageal tumors from 94 patients were subjected to immunohistochemical staining with a monoclonal antibody against p53 and with the monoclonal antibody Ki-67. The immunoreactivity against p53 and the proliferative activity of cancer cells were compared with the clinicopathologic findings in each sample. Prognostic factors including p53 status and Ki-67 labeling index (LI; percentage of Ki-67-immunostained cells) were evaluated for 81 surviving patients by univariate and multivariate analysis. Results: The mean Ki-67 LI of 50 p 53-positive patients was higher than that of 44 p53-negative patients (p = 0.009). The Ki-67 LI increased according to the progression of tumors. Overexpression of mutated p53 protein was observed in 40.9% of tumors that invaded to the submucosa, and this percentage was not significantly changed in tumors with invasion to the adventitia. Metastases to the regional lymph nodes were observed in 3 of 22 patients with tumors that invaded to the submucosa, and these 3 tumors had both overexpression of mutated p53 protein and high Ki-67 LI. In 81 surviving patients, only lymph node metastasis (p = 0.045) and the curability of tumors (p < 0.001) were identified as independent prognostic factors by multivariate analysis. Conclusions: Overexpression of mutated p53 protein is detected in the early stage of esophageal cancer. This mutated p53 protein may not play an important role for tumor invasion. When tumor invasion is limited to the submucosa, cancer cells that overexpress mutated p53 protein may acquire high proliferative activity. Such cells might have considerable potential for metastasis to the lymph nodes.