Rugge M, Bersani G, Bertorelle R, Pennelli G, Russo V M, Farinati F, Bartolini D, Cassaro M, Alvisi V
Department of Oncology and Surgical Sciences, University of Padova, I-35121 Padova, Italy.
J Clin Pathol. 2005 Aug;58(8):805-10. doi: 10.1136/jcp.2004.025676.
BACKGROUND/AIMS: In the natural history of gastric cancer, non-invasive neoplasia (NiN) precedes invasive carcinoma. A histological classification of gastric NiN has recently been proposed by a World Health Organisation international panel of experts. Genetic instability is known to be among the molecular pathways involved in gastric oncogenesis. In this retrospective cross sectional study, microsatellite instability (MSI) was analysed in a consecutive series of NiN and NiN related histological alterations from a northern Italian region at high risk for gastric cancer.
PATIENTS/METHODS: Fifty five consecutive cases (indefinite for NiN, 29 cases; low grade NiN, 17 cases; high grade NiN, nine cases) were analysed by radioactive polymerase chain reaction and electrophoresis for microsatellite alterations at six loci (BAT25, BAT26, D2S123, D5S346, D17S250, and D3S1317). MSI was defined according to the Bethesda criteria distinguishing: (1) no instability in the analysed loci; (2) low frequency MSI (MSI-L); and (3) high frequency MSI (MSI-H). Immunohistochemical expression of MLH1 and MSH2 proteins was also analysed in all cases.
Overall, MSI was found in 11 of 55 cases (indefinite for NiN, five of 29 (MSI-L, four; MSI-H, one); low grade NiN, three of 17 (MSI-L, one; MSI-H, two); high grade NiN, three of nine (MSI-L, one; MSI-H, two).
In an Italian high risk area for gastric cancer, MSI is part of the spectrum of genetic alterations in gastric non-invasive neoplasia. In European populations at high risk of gastric cancer, DNA repair system alterations are thought to be among the early molecular events in gastric carcinogenesis.
背景/目的：在胃癌的自然病程中，非侵袭性肿瘤（NiN）先于浸润性癌出现。世界卫生组织国际专家小组最近提出了胃NiN的组织学分类。已知基因不稳定是参与胃癌发生的分子途径之一。在这项回顾性横断面研究中，对来自意大利北部胃癌高风险地区的一系列连续的NiN及与NiN相关的组织学改变进行了微卫星不稳定性（MSI）分析。
患者/方法：对55例连续病例（NiN不确定型29例、低级别NiN 17例、高级别NiN 9例）进行放射性聚合酶链反应和电泳分析，检测6个位点（BAT25、BAT26、D2S123、D5S346、D17S250和D3S1317）的微卫星改变。根据贝塞斯达标准定义MSI，区分：（1）分析位点无不稳定；（2）低频MSI（MSI-L）；（3）高频MSI（MSI-H）。所有病例还分析了MLH1和MSH2蛋白的免疫组化表达。
总体而言，55例中有11例发现MSI（NiN不确定型29例中有5例（MSI-L 4例、MSI-H 1例）；低级别NiN 17例中有3例（MSI-L 1例、MSI-H 2例）；高级别NiN 9例中有3例（MSI-L 1例、MSI-H 2例）。
在意大利胃癌高风险地区，MSI是胃非侵袭性肿瘤基因改变谱的一部分。在欧洲胃癌高风险人群中，DNA修复系统改变被认为是胃癌发生早期的分子事件之一。
