Significance of spontaneous apoptosis during colorectal tumorigenesis.

To determine if apoptosis is involved in colorectal tumorigenesis and its progression, colorectal adenomas (n = 63), carcinomas (n = 49), and normal mucosa were investigated by using in situ end-labeling (TUNEL) method. The expression of Ki-67 was also analyzed immunohistochemically. TUNEL labeling index (TLI) and Ki-67 labeling index (KLI) were determined. TLI/KLI was significantly higher in the adenomas of small size and/or of low and middle grade atypia than those of large size and/or of high grade atypia. No difference was observed in the indices between adenomas and carcinomas and among the cancer groups classified on the basis of their clinicopathological features. The results indicate that the reduction of susceptibility to apoptosis plays an important role in the early stage of the adenoma-carcinoma sequence. Apoptosis can explain the enormous cell loss thought to exist in normal colorectal mucosa and in the tumor growth process.