The incidence of apoptosis during colorectal tumorigenesis

Epithelial homeostasis in colorectal tumorigenesis is dependent not only on the rate of cell production but also on the rate of apoptosis, a genetical ly programmed process of autonomous cell death. Ideally, an analysis of cel l kinetics should be carried out for both cell proliferation and death. We investigated the incidence of apoptosis in 35 colorectal neoplasms (15 aden omas 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 o f oncogene products were analyzed immunohistochemically. When the TUNEL lab eling index (TI) and the Ki-67 labeling index (IU) 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, I(I increased with the progression of colorectal tu morigenesis. Moreover, TI of the carcinomas was significantly higher in c-M yc-positive cases than in c-Myc-negative cases (p<0.05). The results indica te that apoptosis plays an important role in the early stage of the adenoma -carcinoma sequence, permitting us to speculate that the increased tumor ce ll proliferation is negated by increased apoptosis at the stage of adenoma with high-grade dysplasia (or intramucosal carcinoma), while cell prolifera tion overwhelms cell death at the stage of invasive carcinoma.