Kashiwagi K, Watanabe M, Ezaki T, Kanai T, Ishii H, Mukai M, Hibi T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Br J Cancer. 2000 Jun;82(11):1814-8. doi: 10.1054/bjoc.1999.1154.
To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5-7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa.
为了评估微卫星不稳定性（MSI）在慢性胃炎发展为胃腺癌或腺瘤过程中的作用，我们回顾性分析了胃炎、腺瘤和腺癌中五个微卫星位点的突变情况。在不同时期从每位患者的同一部位取胃黏膜活检样本，并检测MSI。55例慢性胃炎患者中只有1例显示MSI-H表型，其余54例患者表现为微卫星稳定（MSS）表型。在17例胃腺瘤或高分化腺癌患者中，有6例表现为MSI阳性表型。有趣的是，所有6例显示MSI的患者，包括3例高水平MSI（MSI-H）病例和3例低水平（MSI-L）病例，在慢性胃炎阶段就已出现MSI。在3例MSI-H病例中的2例，在腺癌最终诊断前1.5至7年的胃炎阶段就观察到了相同的MSI模式。距癌灶10毫米范围内的相邻胃炎黏膜也显示出MSI。35例幽门螺杆菌感染患者中均未发现MSI，但在30例未感染患者中有1例发现了MSI。此外，在慢性胃炎阶段表现为MSI-H的3例胃腺瘤或高分化腺癌病例中，有2例在整个观察期内均无幽门螺杆菌感染的证据。这些结果表明，慢性胃炎阶段活检标本中的MSI可能预测进展为腺瘤和高分化腺癌的风险，并且幽门螺杆菌感染本身可能不会直接在胃黏膜中诱导MSI。
