bcl-2 protein expression in gastric remnant mucosa and gastric cancer 15 or more years after partial gastrectomy.

Partial gastrectomy is a risk factor for subsequent gastric cancer. The genetic alterations associated with malignant transformation, however, are poorly understood. Ninety-eight biopsies from 22 patients with benign gastric mucosa (BGM) at least 15 years after gastrectomy and resected specimens from 13 patients with postgastrectomy stump cancer (GC), were evaluated for immunohistochemical expression of bcl-2 oncogenic protein and correlated with the presence of dysplasia and subtypes of intestinal metaplasia (IM), categorized using high-iron diamine-alcian blue and alcian blue-periodic acid-Schiff stains. In BGM patients, 91% had chronic gastritis with atrophy, 18% showed complete (Type I) IM, 36% showed incomplete (Type II) IM, and 45% Type III IM. Twelve biopsy specimens from nine BGM patients showed mild-to-moderate dysplasia. Increased bcl-2 expression was present in 27% of BGM patients, with a significant association with increasing grade of IM: 20% in specimens with Type I IM, 30% with Type II, and 40% with Type III (P = .01). bcl-2 overexpression was more often present in the area of the anastomosis than in the body or fundus (P = .06). Of GC patients, 15% had Type II IM and 85% Type III IM. Moderate-to-severe dysplasia was present in adjacent benign mucosa in 46%. bcl-2 was present in 54% of GCs, and increased expression was detected in the adjacent benign mucosa in 60%. bcl-2 expression did not correlate with the presence or degree of dysplasia in either BGM or GC patients. bcl-2 protein is frequently expressed in GC. Increased expression is observed in mucosa adjacent to tumor and, to a lesser extent, in biopsy specimens of BGM, often associated with Type III IM. These findings suggest a possible role for the bcl-2 proto-oncogene in malignant progression.