Acceleration of proliferative activity of esophageal squamous cell carcinoma with invasion beyond the mucosa: Immunohistochemical analysis of Ki-67 and p53 antigen in relation to histopathologic findings

Abstract

BACKGROUND: The authors observed patients with superficial esophageal squamous cell carcinoma (s-ESC). Those with cancer invasion beyond the muscularis mucosae (SM-carcinoma) had an extremely poor prognosis, compared with those with intramucosal carcinoma (M-carcinoma). Therefore, we surveyed cell proliferative activities in relation to pathologic findings of the s-ESC. METHODS: p53 protein expression and Ki-67 labeling index (LI) were surveyed with detailed pathologic examinations of 75 s-ESC lesions from 70 patients who underwent esophagectomy. The results were compared by statistical analysis using the chi-square test and unpaired Student's t-test. RESULTS: p53 protein expression was observed in 57.3% of the patients with s-ESC. The frequency and intensity of its accumulation correlated with the depth of cancer invasion and was markedly elevated in invasion beyond the muscularis mucosae. The LI of Ki-67 positive nuclei was also increased with cancer invasion. The values in the intraepithelial carcinoma and in carcinoma with invasion to the muscularis mucosae were 48.5 +/- 13.7% [mean +/- standard deviation (SD)] and 66.6 +/- 12.9%, respectively, and the difference is significant, P < 0.01. In the SM-carcinomas, the LIs of Ki-67, with or without lymph node metastasis, were 73.5 +/- 10.0% and 64.4 +/- 11.3%, respectively, and the former was higher than the latter with a significant difference, P < 0.05. CONCLUSIONS: Cancer cell proliferative activities were markedly accelerated in s-ESC cases with cancer invasion beyond the muscularis mucosae and lymph nodal involvement, which was associated with a poorer prognosis of the SM-carcinoma compared with the M-carcinoma, and must be one of the important indices to decide the indication of local resection for s-ESC.