十二指腸の腫瘍様病変と上皮性腫瘍におけるGNAS遺伝子解析

GNAS Mutations in the Tumor-like Lesions and Tumors of the Duodenum

要旨●十二指腸に発生する良性上皮性病変と腫瘍に対して，GNAS，KRAS，BRAF遺伝子変異検索を行った．良性病変については臨床病理学的事項についても検討した．胃腺窩上皮化生，異所性胃粘膜，幽門腺腺腫，腸型腺腫，腺癌はGNAS変異をそれぞれ41％，28％，92％，0％，17％に認め，KRAS変異をそれぞれ26％，2％，42％，20％，37％に認めた．BRAFは胃腺窩上皮化生の1例のみ変異を認めた．異所性胃粘膜3例で，胃腺窩上皮化生部分と胃底腺部分で共通のGNAS変異が認められた．腺癌に対する免疫染色では，GNAS変異陽性例ではMUC5ACが有意に強陽性を示し，CDX2が陰性もしくは弱陽性となる傾向を示した．以上より，十二指腸の胃腺窩上皮化生や異所性胃粘膜が幽門腺腺腫や腺癌の前駆病変である可能性が改めて示唆された．

　We analyzed GNAS, KRAS, and BRAF mutations in tumor-like lesions and tumors of the duodenum. We also analyzed clinicopathological findings of the benign tumor-like lesions. GNAS mutations were identified in 41% of GFM（foveolar gastric metaplasia）, 28% of GH（gastric heterotopia）, 92% of PGA（pyloric gland adenoma）, 0% of intestinal-type tubular adenoma, and 17% of adenocarcinoma cases and KRAS mutations were found in 26% of FGM, 2% of GH, 42% of PGA, 20% of intestinal-type tubular adenoma, and 37% of adenocarcinoma cases. A BRAF mutation was found in only one GFM lesion（2%）. We performed mutational analysis of the presence of genetic alterations in two epithelial components：foveolar epithelium and oxyntic glands ; we identified similar GNAS mutations in all cases. We further performed immunohistochemical analysis of the 20 adenocarcinoma cases. Adenocarcinoma with GNAS mutations tested significantly positive for MUC5AC and significantly negative for CDX2. Therefore, GFM and GH might be potential precursors of duodenal tumors.