Aberrant crypt foci: what we know and what we need to know

Aberrant crypt foci (ACF) have emerged as a putative precursor to colorectal adenomas and are a potential biomarker for colorectal carcinoma. In this review, we describe the histologic and endoscopic characteristics of human ACF, summarize the identified genetic abnormalities, and examine the evidence for using ACF as a biomarker for colorectal carcinoma. The published literature on aberrant crypt foci was identified using a MEDLINE/PubMed search with a secondary review of cited publications. Epidemiologic studies support a role for ACF in the adenoma-carcinoma sequence. Genetic abnormalities that occur in and are characteristic of colorectal carcinoma have been described in ACF. Although chromoendoscopy with magnification colonoscopy can identify human ACF in vivo, standardization of the definition and of the technique for endoscopic identification and classification is needed. Studies of reproducibility, interobserver variability, and continuity over time to validate ACF as a clinical end point are required. ACF hold promise as a biomarker for colorectal carcinoma, but additional study is needed.