The adenoma carcinoma sequence in colorectal neoplasia

Knowledge of the biological events involved in colorectal tumor formation is progressing rapidly. Molecular studies support the clinical impression that adenocarcinoma of the large intestine develops in stages. At the center of the pathological continuum between normal mucosa and invasive carcinoma is the premalignant lesion, the adenomatous polyp. We review the epidemiological, morphological, biochemical, and genetic evidence implicating adenomas as precursors of colorectal carcinoma. The molecular changes most highly implicated in neoplastic initiation and progression are reviewed in detail. Current strategies of chemoprevention are summarized, and future prospects for clinical intervention are outlined.