The colorectal adenoma-carcinoma sequence

Background: It is widely accepted that the adenoma-carcinoma sequence represents the process by which most, if not all, colorectal cancers arise. The evidence supporting this hypothesis has increased rapidly in recent years and the purpose of this article is to review this evidence critically and highlight its clinical significance. Methods: Medline searches were used to identify recent key articles relating to the adenoma-carcinoma sequence. Further pertinent articles were obtained by manual scanning of the reference lists of identified papers. Results: The evidence supporting the adenoma-carcinoma sequence can be classified as epidemiological, clinicopathological and genetic. The most recent and largest body of data relates to molecular genetic events and their cellular effects; however, many other approaches, such as cytogenetics, molecular cytogenetics and cytometry, have also yielded valuable information. Conclusion: Recent work continues to support the adenoma-carcinoma sequence, but there is a paucity of data on the interrelationship between different genetic mutations and on the relationship between molecular and other types of genetic abnormalities. The clinical utility of the observations described has yet to be fully realized and global genetic analysis of colorectal tumours may prove to be central in rational adenoma management.