Apoptotic cell death and its relationship to carcinogenesis in colorectal carcinoma

Abstract

Apoptotic cell death plays an important role in the proliferation and turnover of cells in various tumors. The relationship between apoptosis and cell proliferation was studied to determine each of their roles in colorectal carcinogenesis. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The occurrence of apoptosis was examined in colorectal cancer that had invaded the submucosa. Specimens were obtained from 38 cases of cancer with adenoma and 29 cases of cancer de novo. Apoptotic indices (AIs) as percentages of TUNEL-positive cells relative to the number of tumor cells and Ki-67 labeling indices (PI) were investigated. The relationship between the frequency of apoptosis and the expression of p53 and c-myc proteins was also investigated. In cancer with adenoma, the ratio of AI/PI in adenoma cells was significantly higher than that of cancer cells (P < 0.0001). Mean AIs of cancer with adenoma were significantly higher than those of cancer de novo particularly in the flat-type cancers (P < 0.05). Among p53 negative tumors, the ratio of AI/PI for cancer de novo was significantly lower than that for cancer with adenoma (P < 0.05). AI of cancer de novo was lower than that of cancer with adenoma in cases with overexpression of c-myc protein (P < 0.05), whereas there was no significant difference in the ratio of AI/PI between cancer de novo and cancer with adenoma. Colorectal carcinogenesis is related to the inhibition of apoptosis and to the augmentation of proliferative activity both in cancer with adenoma and in cancer do novo. A reduction of the rate of apoptosis as compared with that of cell proliferation might explain the rapid-growing nature of cancer de novo particularly in cases with the flat-type appearance.