Abstract
Aberrant crypt foci (ACF) are the earliest histopathologic lesion associated with colorectal cancer. ACFs are commonly used as a surrogate marker for colorectal cancer chemoprevention studies in rodents and, more recently, in humans. However, ACF prevalence in unselected populations is not known, nor which ACF features are important for predicting polyp histopathology. To address these questions, we did magnification chromo-colonoscopy on all patients undergoing routine colorectal cancer screening over a 31-month period. ACFs were classified by location, size (small, <20 crypts/ACF; medium, 20-100 crypts/ACF; large, >100 crypts/ACF), and whether they were elevated above the tissue plane. Overall, 802 magnification chromo-colonoscopies with ACF enumeration were done. Mean patient age was 58.6 +/- 8.5 years, of whom 56% were female, 58% were African American, 21% were Caucasian, and 16% were Latino. Total ACF number, along with increasing ACF size and elevation, correlated with the presence of distal hyperplastic polyps and were higher in African Americans. In contrast, ever-smaller ACFs correlated with the presence of distal adenomas and were independent of age and race. The odds ratio for patients with >or=6 small ACFs and adenomas was 6.02 (95% confidence interval, 2.64-13.70) compared with patients with <or=5 small ACFs, whereas the odds ratio for patients with >or=1 large ACF and hyperplastic polyps was 5.88 (95% confidence interval, 3.00-11.67) compared with patients with none. Small flat ACFs correlate with the presence of distal adenomas, whereas large raised ACFs correlate with the presence of hyperplastic polyps.
Highlights
Aberrant crypt foci (ACF) are believed to be the earliest histopathologic lesion associated with malignant transformation in the colon
All patients were initially seen in the University of Illinois at Chicago (UIC) Colorectal Cancer Screening Clinic, the majority of whom were internal to the UIC clinic system and referred from General Internal Medicine or Family Practice clinics
1,385 patients were seen in the UIC Screening Clinic, of whom 1,054 (76.1%) agreed to allow their information to be collected in our ACF database
Summary
Aberrant crypt foci (ACF) are believed to be the earliest histopathologic lesion associated with malignant transformation in the colon. These structures were initially identified by Bird in 1987 in carcinogen-treated mice [1] and were characterized as z1 crypts that were larger and thicker and which stained more intently than adjacent normal structures [2]. Ex vivo studies have identified more ACFs in patients with a genetic predisposition to polyp syndromes such as familial adenomatous polyposis [2, 3] or a prior history of colorectal cancer [2, 3] compared with patients undergoing colectomy for reasons unrelated to malignancy. Hurlstone et al [8] found increased numbers of ACF in patients with flat adenomas and cancers and suggested that patients with increased numbers of ACFs might need to be surveyed more frequently than is otherwise recommended [9]
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