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

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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. Cancer 1996;77:843‐9.