Activating GNAS and KRAS mutations in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum

• Published in: British journal of cancer 2015-04, Vol.112 (8), p.1398-1404
• Main Authors: Matsubara, A, Ogawa, R, Suzuki, H, Oda, I, Taniguchi, H, Kanai, Y, Kushima, R, Sekine, S
• Format: Article
• Language: English
• Subjects: 631/208/737; 692/699/1503/1504; 692/699/67/68; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Biopsy; Cancer; Cancer Research; Chromogranins; Drug Resistance; Duodenal Neoplasms - genetics; Duodenal Neoplasms - pathology; Endoscopy; Epidemiology; Genetics and Genomics; GTP-Binding Protein alpha Subunits, Gs - genetics; Humans; Hyperplasia; Inflammation; Medical research; Middle Aged; Molecular Medicine; Mutation; Neutrophils; Oncology; Polyps; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Sequence Analysis, DNA; Small intestine; Stomach Diseases - genetics; Stomach Diseases - pathology; Tumors; Ulcers
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.104

Background: Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds. Methods: We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS , KRAS, and BRAF mutations. Results: Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS -mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation. Conclusions: A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours.