Aberrant crypt foci: are they intermediate endpoints of colon carcinogenesis in humans?

Abstract

There is a wealth of literature, both from epidemiological and molecular studies, which support the role of aberrant crypt foci (ACF) as a putative precursor to colorectal adenomas and a potential biomarker for colorectal carcinoma. In this review, we critically examine the evidence on employing ACF as an intermediate endpoint. Recent, larger-scale, multicenter studies of ACF have raised questions about ACF. The prevalence of ACF has not correlated with colorectal adenomas, and the technique for ACF detection using high-magnification chromoendoscopy has demonstrated considerable variability across endoscopists and over time. Dysplastic ACF, once postulated as the ACF destined for adenomatous transformation, have been rarely identified in US individuals, in contrast to European and Japanese investigations. A substantial percentage of purported, endoscopically detected ACF have not been confirmed on histologic review. Finally, molecular characterization of ACF has been studied on only a limited basis. ACF remain a potential biomarker for colorectal cancer, but similar to other biomarkers under development, additional study of ACF is needed before reliable, clinical application can be assured.