Epithelial homeostasis in colorectal tumorigenesis is dependent not only on the rate of cell production but also on the rate of apoptosis, a genetically programmed process of autonomous cell death. Ideally, an analysis of cell kinetics should be carried out for both cell proliferation and death. We investigated the incidence of apoptosis in 3 5 colorectal neoplasms (1 5 adenomas and 20 carcinomas) using the DNA nick end labeling method (TUNEL). The expression of Ki-67 as a marker of proliferating activity and some kinds of oncogene products were analyzed immunohistochemically. When the TUNEL labeling index (TI) and the Ki-67 labeling index (KI) were determined, TI was found to be significantly higher in adenomas with high-grade dysplasia (TI: 2.5%) than in adenomas with low-grade dysplasia (TI: 0.6%) or carcinomas (TI: 1.4%). In contrast, KI increased with the progression of colorectal tumorigenesis. Moreover, TI of the carcinomas was significantly higher in c-Myc-positive cases than in c-Myc-negative cases (p<0.05). The results indicate that apoptosis plays an important role in the early stage of the adenoma-carcinoma sequence, permitting us to speculate that the increased tumor cell proliferation is negated by increased apoptosis at the stage of adenoma with high-grade dysplasia (or intramucosal carcinoma), while cell proliferation overwhelms cell death at the stage of invasive carcinoma.
