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Patchy Field Defects of Apoptosis Resistance and Dedifferentiation in Flat Mucosa of Colon Resections From Colon Cancer Patients

From the Departments of Microbiology and Immunology (HB, HH, CMP, CB), Surgery (JAW), Medicine (HG, DLE), and Pharmacology and Toxicology (ELJ), the College of Public Health (DJR), and the Arizona Cancer Center (HB, JAW, HG, DLE, CMP, ELJ, HC, DJR), University of Arizona, Tucson, Arizona; the Tucson Veterans Affairs Hospital (HG), Tucson, Arizona; and the Cancer Center (ELJ), University of Kentucky, Lexington, Kentucky.

Correspondence: Address correspondence and reprint requests to: Carol Bernstein, PhD, Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, AZ 85724; Fax: 520-626-2100; E-mail: bernstein3@ earthlink.net.

Background: Abnormal areas in normal-appearing flat colonic mucosa (field defects) may predispose individuals to colon cancer. Markers of field defects would indicate cancer risk.

Methods: We evaluated apoptosis capability, dedifferentiation, frequency of simple aberrant crypts, aberrant crypt foci, microadenomas, and total nicotinamide adenine dinucleotide levels at locations within normal-appearing flat mucosa obtained from colon resections.

Results: Among goblet cells from colonic mucosa samples of individuals without colonic neoplasia, there was a high mean deoxycholate-induced apoptotic index (AI) of 59.1% and high Dolichos biflorus agglutinin (DBA) lectin reactivity (differentiation) in 85.0% of samples. In contrast, flat mucosa samples from colon cancer patients had a significantly (P < .01) lower average AI of 37.4%, and a significantly (P = .03) lower percentage (40.5%) had high DBA reactivity. For colon cancer patients, AI and DBA reactivity values were patchy within a resection. Nicotinamide adenine dinucleotide levels were highly variable among individuals without neoplasia, and aberrant crypt foci and microadenomas were rare.

Conclusions: AI and aberrant DBA reactivity are promising indicators of colon cancer risk. Our results attest to the importance of obtaining multiple samples to assess colon cancer risk because of the patchy nature of field defects.

Key Words: Field defects • Apoptosis resistance • Differentiation • Colon cancer • Dolichos biflorus agglutinin

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