An evaluation of rectal epithelial proliferation measurement as biomarker of risk for colorectal neoplasia and response in intervention studies.

: Colorectal carcinogenesis is preceded by a phase of epithelial hyperproliferation. Detection and measurement of this hyperproliferation could be useful as a marker of risk for neoplasia or a measure of response to intervention therapy. Today, bromodeoxyuridine labelling and immunohistology is the easiest to perform and most standardized technique for evaluating proliferation in experimental and human studies. In general, measurement of proliferation has fulfilled expectation in experimental studies, however, in humans it has been less conclusive. The reasons are multifactorial and include: limitations in obtaining tissue samples and sampling error, the type of labelling technique used, lack of an objective method for quantifying proliferation and confounding factors influencing the degree of proliferation. The use of matched controls, sophisticated statistical analysis and the search for trends and not just statistical significance, is to be recommended. At present, evaluation of rectal epithelial proliferation is of limited value in assessing risk for colorectal neoplasia in the individual. On the other hand, it seems a useful biomarker of response within the context of a matched control intervention trial.