CLINICOPATHOLOGICAL SIGNIFICANCE OF THE EXPRESSION OF MUTATED P53 PROTEIN AND THE PROLIFERATIVE ACTIVITY OF CANCER-CELLS IN PATIENTS WITH ESOPHAGEAL SQUAMOUS-CELL CARCINOMA

Background: The aim of this study was to investigate the relation betw een the expression of mutated p53 protein and the proliferative activi ty of cancer cells in esophageal squamous cell carcinoma. In addition, the clinical and biologic significance of p53 status and the prolifer ative 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 incl uding p53 status and Ri-67 labeling index (LI; percentage of Ki-67-imm unostained cells) were evaluated for 81 surviving patients by univaria te and multivariate analysis. Results: The mean Ki-67 LI of 50 p53-pos itive patients was higher than that of 44 p53-negative patients (p = 0 .009). The Ki-67 LT 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 significant ly changed in tumors with invasion to the adventitia. Metastases to th e regional lymph nodes were observed in 3 of 22 patients with tumors t hat invaded to the submucosa, and these 3 tumors had both overexpressi on 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 multiv ariate analysis. Conclusions: Overexpression of mutated p53 protein is detected in the early stage of esophageal cancer. This mutated p53 pr otein may not play an important role for tumor invasion. When tumor in vasion is limited to the submucosa, cancer cells that overexpress muta ted p53 protein may acquire high proliferative activity. Such cells mi ght have considerable potential for metastasis to the lymph nodes. (C) 1997 by the American College of Surgeons.