Biology and diagnosis of aberrant crypt foci

Aberrant crypt foci (ACFs) are clusters of colonic crypts that can be identified after staining and that have a different behaviour than the surrounding crypts. They have been hypothesized to be the potential precursors of colonic neoplastic lesions. Since they are detectable in vivo with endoscopic stains, they have been proposed as early biomarkers for colonic carcinogenesis. Our aim was to examine the literature regarding the role of ACFs in the pathogenesis of colorectal cancer (CRC).

An intensive PubMed search was performed with the following terms: aberrant crypt foci, colorectal cancer, biomarker, carcinogenesis.

Aberrant crypt foci have a variable prevalence and little is known about their natural history. They can be classified as hyperplastic or dysplastic. There is evidence that supports their role as preneoplastic lesions and features detectable by chromoendoscopy have been related to CRC risk. Moreover, ACFs have been shown to harbour genetic and epigenetic alterations common in adenomas and CRC. However, contradictory results have been obtained and difficulties in endoscopic detection and characterization have been described in large-scale studies.

Despite the inconsistencies in ACF detection and characterization, several genetic and epigenetic changes common in both ACFs and CRC have been verified throughout the studies. This evidence is increasingly strong and it grows along with progress in the knowledge of carcinogenesis molecular pathways. Clinical application of ACFs as an intermediate endpoint for colorectal carcinogenesis is under development and a deeper knowledge of cancer mechanisms is needed before it can be applied or discarded.