Are aberrant crypt foci putative precursor lesions of colorectal cancer: a pilot study

colorectal cancer (CRC) is the second most often diagnosed cancer in
westernized nations. Aberrant crypt foci (ACF) may represent the earliest
precursor lesions in CRC development. Although CRC, adenoma and ACF share same
genetic and epigenetic alterations, other links remain to be established
between features of colonic malignant tumor, their adenomatous precursors, and
ACF, before they are acknowledged as the earliest form of colonic
transformation.
The adenomatous polyposis coli and β-catenin genes are the two major components
of the Wnt signaling pathway that has been shown to play an important role in
the formation of certain cancers. The overactivation of the pathway, which
results in abnormal accumulation of beta-catenin protein in nuclei, contributes
to most CRCs, both sporadic and hereditary.
We propose that the investigation of normal colonic tissue and ACF for target
genes of the Wnt signaling in different patient groups, stratified for
CRC-risk, may aid in understanding whether a subset of ACF are likely to
progress to cancer and whether this has clinical implications.

1) to sample ACF in colorectal mucosa of patients without an increased risk of
CRC, patients at an increased of recurrent advanced adenoma based on a personal
history of adenomas, patients with established CRC and patients with HNPCC and
to determine whether the number of ACF discriminates among different patient
groups stratified by CRC-risk. 2) To understand whether aberrations of
regulation of *Wnt signaling* could identify ACF that are likely to progress to
cancer.

ACF will be discriminated in colonic mucosa by endoscopy during high-resolution
close-focus chromoendoscopy. Colonic mucosa will be stained during colonoscopy
using indigo carmine to accentuate the contours of ACF. During endoscopy,
biopsies are taken from ACF, (but also from CRC if present) and from matched
normal mucosa, in different groups of patients according to CRC-risk. The
obtained biopsies will be processed and Wnt signaling will be studied using
confocal microscopy.

The burden associated with participation in this study is minor. The are very
small extra risks due to taking extra biopsies.