Abstract
Aberrant crypt foci (ACF) are putative preneoplastic lesions that occur in the colons of rodent tumor models and are abundant in the colorectum of humans. Although their presence within the colonic mucosa is incontrovertible, their clinical significance remains a source of controversy. In the following presentation, we will review the history of ACF from their first identification in rodent carcinogen models to their identification and characterization in human colons. In order to better define ACF, one must consider their histopathology, and, here, the difference between rodent and human is striking. Whereas in the rodent a single crypt can acquire dysplastic features, such is not the case in human where ACF as large as 50–100 crypts across are rarely dysplastic. In over 1500 lesions we have examined from approximately 500 patients, we observe that if endoscopic criteria are strictly adhered to, ACF are almost always hyperplastic lesions, with either a “distended” or “serrated” appearance when studied en face. We and others have clearly identified a number of colon cancer risk factors that also associate with at least the density of ACF in the distal 20 cm of colorectum. These risk factors include central obesity, increased bioavailability of IGF‐1, prior or synchronous colon neoplasia, family history of colonic neoplasia and cigarette smoking. In fact, a history of 20 pack‐years or more of smoking is associated with an increased likelihood (adjusted OR=3.45; 95% CI 1.93–6.18) of having more than the median number of ACF (≥ 15) compared to non‐smokers (Anderson et al., under review). Considering their prevalence in the colons of cancer patients, their corresponding association with a panel of key colon cancer risk factors and their cancer‐related molecular aberrations, we argue that these lesions may provide an important signal of one or more risk factors, and are likely part of the ‘field effect’ within the colonic mucosa. If a clearer association can be established with high‐grade adenomas, we believe ACF will ultimately be of great utility as surrogate markers for cancer prevention studies.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL02-05.
RSS Feeds