Immunohistochemical and Molecular Features of Gastric Hyperplastic Polyps

Abstract

1.1.Context:Gastric hyperplastic polyps are generally considered to be inflammatory lesions that develop in association with gastritis. Large polyps may contain foci of dysplasia, suggesting that they represent neoplasms, although molecular data regarding their pathogenesis are lacking. 1.2.Objective:To describe the clinical, pathologic, and molecular features of large (>1 cm) gastric hyperplastic polyps and compare them to those of small (≤1 cm) hyperplastic polyps and gastric adenomas. 1.3.Design:15 large hyperplastic polyps (>1 cm), including 4 with dysplastic foci, 10 small hyperplastic polyps (≤1 cm), and 9 gastric adenomas were evaluated for immunohistochemical expression of MGMT, MLH-1, β-catenin, p27, p16, and p53. Polyps with dysplasia or abnormal β-cateninexpression were assessed for APC and β-catenin (CTNNB1) mutations. Large hyperplastic polyps and adenomas were analyzed for KRAS and BRAF mutations. 1.4.Results:Complete loss of MGMT expression was significantly more frequent in large hyperplastic polyps (47%), often in combination with loss of p27 (47%), compared to adenomas (0% and 0%, p=0.02, respectively) and smaller lesions [0% (p=0.02) and 10% (p=0.09), respectively]. All non-dysplastic hyperplastic polyps showed preserved MLH1 and lacked nuclear β-catenin staining, but 3 with dysplasia had APC or β-catenin mutations. KRAS or BRAF mutations were detected in 20% of large hyperplastic polyps and 11% of adenomas. Most polyps were entirely negative for p16, although 6 (40%) large hyperplastic polyps and 3 (33%) adenomas showed expression in 10% p53 expression in the epithelium. Conclusion:Small gastric hyperplastic polyps are likely non-neoplastic, reparative lesions, but large polyps often show immunohistochemical and molecular abnormalities such as concomitant loss of MGMT with p27 staining, APC or β-cateninmutations in areas of dysplasia, and KRAS or BRAF mutations. These findings raise the possibility that some large hyperplastic polyps of the gastric mucosa represent early neoplasms.