Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.
J Pathol. 2013 Mar;229(4):579-87. doi: 10.1002/path.4153. Epub 2013 Feb 4.
Gastric and duodenal adenomas exhibit a significant morphological and phenotypical diversity and are classified into intestinal-type, foveolar-type and pyloric gland adenomas. We analysed the mutations in GNAS, KRAS, BRAF and CTNNB1 and the expressions of mismatch repair (MMR) proteins in 80 gastric and 32 duodenal adenomas with histologically distinct subtypes, as well as in 71 gastric adenocarcinomas. Activating GNAS mutations were found in 22 of the 35 pyloric gland adenomas (PGAs; 63%) but in none of the foveolar-type or intestinal-type adenomas or the adenocarcinomas. Fourteen PGAs (41%), two foveolar-type adenomas (9%), five intestinal-type adenomas (9%) and one adenocarcinoma (1%) had KRAS mutations. BRAF mutations were absent in all the adenomas and adenocarcinomas that were examined. CTNNB1 mutations were only found in two intestinal-type adenomas (4%). Notably, 13 of the 14 KRAS-mutated gastric and duodenal PGAs had concurrent GNAS mutations. The loss of the MMR proteins, which is indicative of microsatellite instability, was observed in one PGA (3%), 12 foveolar-type adenomas (52%), one intestinal-type adenoma (2%) and five adenocarcinomas (7%). These observations indicate that each histological subtype of gastric and duodenal adenomas has a distinct genetic background. In particular, the present study identified the frequent presence of activating GNAS mutations, which are often associated with KRAS mutations, as a characteristic genetic feature of PGAs of the stomach and duodenum.
胃和十二指肠腺瘤表现出显著的形态和表型多样性，并被分为肠型、滤泡型和幽门腺腺瘤。我们分析了 80 例胃和 32 例十二指肠具有不同组织学亚型的腺瘤以及 71 例胃腺癌中 GNAS、KRAS、BRAF 和 CTNNB1 的突变以及错配修复（MMR）蛋白的表达。在 35 例幽门腺腺瘤（PGA；63%）中发现了激活的 GNAS 突变，但在滤泡型或肠型腺瘤或腺癌中均未发现。14 例 PGA（41%）、2 例滤泡型腺瘤（9%）、5 例肠型腺瘤（9%）和 1 例腺癌（1%）有 KRAS 突变。在所有被检测的腺瘤和腺癌中均未发现 BRAF 突变。CTNNB1 突变仅在 2 例肠型腺瘤（4%）中发现。值得注意的是，在 14 例 KRAS 突变的胃和十二指肠 PGA 中，有 13 例同时存在 GNAS 突变。在 1 例 PGA（3%）、12 例滤泡型腺瘤（52%）、1 例肠型腺瘤（2%）和 5 例腺癌（7%）中观察到 MMR 蛋白缺失，表明微卫星不稳定。这些观察结果表明，胃和十二指肠腺瘤的每种组织学亚型都具有独特的遗传背景。特别是，本研究确定了激活的 GNAS 突变的频繁存在，其通常与 KRAS 突变相关，是胃和十二指肠 PGA 的特征性遗传特征。
