胃癌和肠化上皮组织微卫星不稳定性及bcl-2、erbB-2和p53蛋白表达的比较研究

Comparative study of microsatellite instability and expression of bcl-2,erbB-2 and p53 protein in gastric carcinoma and gastric epithelium with intestinal metaplasia

目的：研究微卫星不稳定性（MSI）在胃癌发生中的作用及其与bcl－2、erbB－2和突变型p53蛋白表达的关系。方法：采用PCR－SSLP和免疫组织化学技术检测了50例手术切除胃癌和15例肠化组织标本的MSI和bcl－2、erbB－2及突变型p53蛋白表达。结果：胃癌MSI发生率为54％，肠化组织MSI发生率为20％，胃癌组织bcl－2、erbB、及p53蛋白阳性率分别为60％、22％和38％，肠化生组织bcl－2蛋白表达阳性率为53．3％，而p53和erbB－2均为阴性。高中分化腺癌MSI发生率（86．7％）显著高于低分化腺癌（38．7％）（P＜0．05），肠型胃癌MSI发生率（77．8％）显著高于胃型胃癌（40％）（P＜0．05）；MSI与胃癌患者年龄、性别、肿瘤的部位、大小、淋巴结转移、浆膜浸润、临床分期及bcl－2、erbB－2和突变型p53蛋白表达无显著相关。结论：MSI在胃癌的发生中可能起重要作用，可能是胃癌发生过程中的一个早期分子改变，其致癌机制不同于bcl－2、erbB－2及p53。

Objective: To investigate the role of microsatellite instability (MSI ) in the development of gastric cancer (GC) and relationship of MSI with the expression of bcl-2, erbB-2 and p53 protein. Materials and methods: MSI and expression of bcl-2, erbB-2 and p53 protein were studied in 50 surgical specimens of GC and 15 specimens of gastric epithelium with intestinal metaplasia (IM ) with PCR-SSLP and immunohistochemistry. Results: MSI occurred in 54% of GC specimens and 20% of IM ones. The expression of . bcl-2,erbB-2 and p53 protein was positive in 60%, 22% and 38% of GC specimens respectively. And in the specimens of IM, only erbB-2 was positive in 8 out of the 15 specimens and both bcl-2 and p53 were negative. The incidence of MSI was significantly higher in moderately-differentiated adenocarcinoma than in poorly-differentiated one (P ＜0. 05 ). There was no significant correlation of MSI to the age and sex of the patient and the site, size, lymph node metastasis, serosa invasion and stage of GC and to the expression of bcl-2, erbB-2 and p53 protein. Conclusion: MSI is an early molecular marker of GC and likely to play an important role in the development of GC. Nevertheless, it exerts its effects through a different mechanism from that of bcl-2,erbB-2 and p53 genes.