Demonstration of a Field Defect in Gastric Intestinal Metaplasia by Biological Marker Analysis

Gastric intestinal metaplasia (GIM) is a precursor lesion for gastric cancer. It most frequently involves the antrum and the angularis. At endoscopy, it is not possible to visually distinguish GIM from normal stomach. Furthermore, GIM frequently has a patchy distribution with areas of metaplasia coexisting with adjacent areas of other histologies, including normal stomach. In this study we sought to determine whether a “field defect” could be demonstrated in subjects with GIM, involving the entire region of the stomach. The biologic markers tested were ornithine decarboxylase (ODC) activity and bromodeoxyuridine labeling index (LI). Antral biopsies were obtained from 13 subjects with known GIM and 9 controls (no GIM based on multiple biopsies and absence of methylene blue staining). Three adjacent biopsies were obtained for ODC, LI, and histology. Group I consisted of a set of 3 biopsies from the 9 controls. In the 13 subjects with GIM, 2 sets of 3 biopsies were taken with methylene blue guidance in an attempt to obtain both GIM-free (group II) and GIM- containing (group III) tissue. ODC activities were markedly and statistically significantly (P = 0.0001) elevated in groups II and III versus group I; the mean ± SDs were 0.075 ± 0.117 for group I, 1.20 ± 0.83 for group II, and 1.14 ± 0.76 for group III. Group II versus Group III values were not different (P = 0.979). LI was less discriminatory with more overlap between the groups. The highest LI was in group II, which was significantly different from group I (P = 0.014) and group III (P = 0.006). LI values expressed as percentages were 3.9 ± 2.0 for group I, 9.5 ± 5.8 for group II, and 4.2 ± 2.8 for group III. Subjects with the gastric cancer precursor lesion GIM have a field defect demonstrated by increased ODC activity, whether or not the actual biopsy specimen assayed contains metaplasia. LI is highest in biopsies lacking metaplasia from subjects with GIM elsewhere but is not as “discriminatory” as ODC activity. Biological marker analysis, particularly reduction in ODC activity, may serve as a useful marker in gastric cancer prevention trials.