Change of apoptotic status in the human colorectal adenoma-carcinoma sequences and its correlation with carcinogenesis and prognosis

Objective To assess apoptotic status during the development of colorectal cancer and its prognostic value. Methods The apoptotic frequency of 168 fresh adenocarcinoma specimens and primary cultured cells at 2, 12, 24 and 48 hours (9 normal mucosa, 4 adenomas and 9 adenocarcinomas) were measured by flow cytometry (FCM).Apoptotic indices (AI) in situ for 25 adenomas and 77 adenocarcinomas were visualized by TdT-mediated dUTP nick end labeling (TUNEL), Ki-s5 labeling indices (KI), bcl-2, bax, waf1 and p53 were immunostained with ABC method. Results The culture-related apoptosis at 24-48 hours in vitro was obviously decreased in cultured tumor cells when compared with mucosa cells.Spontaneous apoptosis in situ occurred more frequently in tumor with aneuploid type at late stage.There was positive relationship between apoptosis and proliferative activity, determined by both TUNEL and FCM methods.The well-differentiated or early stage lesions with intensive bcl-2/bax expression were significantly more likely to have low AI.p53 accumulation and waf1 depression were mainly related to KI, whereas bax and waf1 overexpression led to a comparatively higher AI/KI ratio.bcl-2 and KI were found to be independent risk factors. Conclusions The data suggest that the depressed susceptibility to inductive apoptosis may contribute to the initial phase of tumorigenesis, and spontaneous apoptosis in vivo may serve as a marker of tumor progression.The bcl-2 and KI may be valuable in predicting prognosis in colorectal cancer.