Apoptosis occurs more frequently in metastatic foci than in primary lesions of human colorectal carcinomas: analysis by terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling.

We examined the occurrence of apoptotic cell death in 15 advanced colorectal carcinomas with lymph-node and/or liver metastases by terminal-deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). TUNEL-positive cells were used to quantify the apoptotic index (AI: percentage of TUNEL-positive cells in carcinomatous cells). Similarly, Ki-67-positive cells were used to quantify Ki-67 labeling (KI: percentage of Ki-67-positive cells in carcinomatous cells) as a proliferative index. The mean AIs of primary colorectal carcinomas, lymph-node and liver metastases were 3.5%, 5.6% and 6.2% respectively. There was a significant group difference between primary carcinomas and lymph-node or liver metastases. The mean KIs of primary colorectal carcinomas, lymph-node and liver metastases were 51.8%, 60.1% and 61.7% respectively. There was a significant group difference between primary carcinomas and lymph-node or liver metastases. In addition, there was a close positive relationship between the AI and MI per specimen. There was no apparent correlation between AI or MI and the expression of nuclear p53 of cancer cells. These results suggested that cell proliferation and loss (apoptosis) were more frequent in metastatic foci than in primary lesions, and that apoptosis might reflect not only cell loss but also the proliferative activity of human colorectal carcinomas.