胃癌组织中环氧合酶-2和hMLH1及hMSH2 蛋白表达与微卫星不稳定的关系

目的 观察环氧合酶-2（COX-2）、hMLH1和hMSH2蛋白在胃癌组织中的表达,探讨其与微卫星不稳定（MSI）的关系。方法 采用Western blot和PCR技术,检测30例胃癌及相应癌旁正常组织COX-2、hMLH1和hMSH2蛋白表达及5个位点的MSI状态。结果 胃癌组织COX-2高表达率为66．7％,hMLH1、hMSH2低表达率分别为40．0％和33．3％,与癌旁正常组织差异均有统计学意义（P均〈0．05）。30例胃癌组织中微卫譬稳定（MSS）17例,MS1l3例,其中高频率MS1（MSI-H）9例,低频率MSI（MSI-L）4例。9例MS1-H中COX-2、hMLH1和hMSH2低表达者分别为6,8和5例,与MSS组差异均有统汁学意义（P均〈0．05）。结论 散发性胃癌发生过程中可能存在MSI途径。MSI途径常伴有hMI．Hl、hMSH2蛋白表达缺陷,并可能伴有COX-2表达降低。

Expression of cyclooxygenase-2, hMLH1 and hMSH2 proteins, and their relationship with microsatellite instability in gastric carcinoma

OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2), human mut-l homologue 1 (hMLH1) and human mut-s homologue 2 (hMSH2) proteins in human paired gastric carcinoma (GC) and adjacent normal mucosa, and analyze their relationship with microsatellite instability (MSI). METHODS: The protein expressions were examined by western blotting. Five MSI loci were assessed by PCR. RESULTS: In 30 surgically excised GC tissues, the overexpression rate of COX-2, the low expression rate of hMLH1 and hMSH2 were 66.7%, 40% and 33.3%, respectively. Significant differences were found when compared with those of adjacent normal mucosa (P < 0.05). MSI was detected in 13 GC. The number of MSI-H (MSI-High, > or = 2 loci), MSI-L (MSI-Low, only one locus), and MSS (microsatellite stable) were 9, 4 and 17, respectively. The number of low expression rates of COX-2, hMLH1 and hMSH2 in MSI-H were 6, 8 and 5, respectively. There were significant differences compared to that of MSS (P < 0.05). CONCLUSION: The results suggest that microsatellite instability pathway is probably involved in the carcinogenesis of gastric carcinoma, which is frequently accompanied by low expression of hMLH1 and hMSH2, and may be also by low expression of COX-2.