The natural history of colorectal adenomas and early cancer.

Adenomas represent the morphological precursors of the vast majority of colorectal cancers: although every adenoma has the capacity of malignant evolution, most adenomas stabilize their progression or even regress. Pathological factors are predictive of the natural history of adenomas in terms of potential and time interval for becoming malignant. Regression of adenomas is histologically well established, but it is thought to be a dynamic process, with cycling phases of regression and growth. Colorectal carcinoma invading the submucosa but not the muscular layer represents the earliest form of clinically relevant colorectal cancer. Grade of differentiation of carcinoma, lymphovascular invasion, and state of the resection margin predict the risk of metastasis. Microstaging of invasive cancer together with tumuor budding allow the metastatic risk to be further stratified into minimal, low, and high. Two distinct profiles are identifiable in the natural history of cancerous adenomas: blocking the growth of early cancer and allowing its progression towards advanced cancer. Thus, biomarkers to distinguish between progressive and non-progressive pT1 neoplasia are needed.