Changes in apoptosis during the development of colorectal cancer: a systematic review of the literature

The development of colorectal cancer is characterised by an accumulation of molecular genetic alterations causing disorders in cell growth, differentiation and apoptosis. Although changes in apoptosis with colorectal cancer development have been studied extensively, a clear consensus of opinion has not yet emerged. In this review, the literature about changes in the frequency and distribution of apoptosis in tissue sections of normal and neoplastic colorectal tissues was reviewed systematically. Using a PUBMED search, 53 relevant articles were identified. Data from these studies are discussed with respect to the following aspects: methods used to detect apoptotic cell death; frequency and locoregional distribution of apoptosis in normal mucosa, adenomas and carcinomas; the correlation between levels of apoptosis and proliferation and the prognostic significance of the degree of apoptosis in colorectal cancer. Possible underlying mechanisms of dysregulation of apoptosis are discussed briefly. Finally, possible therapeutic implications of knowledge of the molecular regulation of apoptosis are discussed and potential options for further research are suggested. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.