Proliferative activity and p53 protein accumulation correlate with early invasive trend, and apoptosis correlates with differentiation grade in oesophageal squamous cell carcinomas

Using oesophageal squamous cell carcinoma samples of both intramucosal and advanced types, proliferative activity (Ki-67 labelling index), p53 protein accumulation and apoptosis (in situ DNA nick end labelling) were assessed, and the relation of these values to progression or differentiation grade of tumours was analysed. In terms of proliferative activity and the proportion of positive cases with p53 accumulation, a statistically significant difference was demonstrated between intraepithelial carcinomas and intramucosal carcinomas with stromal invasion (17.2% vs 31.7% for the Ki-67 labelling index, and 23.5% vs 67.4% for the proportion of positive cases of p53 accumulation). Values for the latter were almost comparable to those of advanced carcinomas. Immunohistologically, Ki-67 positive, proliferating cells were distributed preferentially in the peripheral fronts of invading nests. Apoptotic cells were observed in the inner areas of the invading nests of the intramucosal carcinomas with stromal invasion and in more advanced lesions, but were rarely observed in the normal epithelium or intraepithelial carcinomas. Apoptotic cells were seen mainly around areas of keratinization, and the apoptotic cell index was higher in well and moderately differentiated types of advanced carcinomas than in the poorly differentiated type (2.59% vs 1.09%). An increase in proliferative activity and an accumulation of p53 protein are associated with the onset of early carcinomatous invasion, while apoptosis is closely linked with the differentiation grade of carcinoma cells.