胃癌形成中COX-2的表达及其与细胞凋亡和增殖的关系

Expression of COX-2 in the Carcinogenesis of Gastric Epithelia and Its Correlation with Cell Apoptosis and Proliferation

目的研究胃癌(GC)形成中环氧合酶-2(COX-2)的表达与其细胞凋亡、增殖的关系,探讨COX-2在GC形成中的可能作用机制。方法采用免疫组化(SABC)法和原位末端标记法(TUNEL)检测15例正常胃黏膜(normalgastricmucosa,NGM)、30例胃粘膜肠上皮化生(IM)、30例异型增生(Dys)和40例GC组织中COX-2、增殖细胞核抗原(PCNA)阳性表达和细胞凋亡情况。结果在NGM→IM→Dys→GC的形成过程中,COX-2的表达呈递增趋势,其阳性表达中GC组(67.5%)和NGM组(13.3%)及GC组和IM组(33.3%)差别均有显著性(P<0.05)。细胞凋亡指数(AI)在GC时最低(2.8±0.6),GC组AI显著低于其他各组(P<0.01)。细胞增殖指数(PI)则呈递增趋势,GC组与各组比较差异有显著性(P<0.01)。在不同程度癌前病变中COX-2的表达差异无显著性(P>0.05)。COX-2在低分化GC中表达显著高于高分化型。COX-2、PI与GC淋巴结转移、血管浸润均密切相关(P<0.05)。从NGM→IM,COX-2与AI呈正相关(r=0.55,P<0.05);从Dys→GC,二者与AI负相关(r=-0.56,P<0.05)。在GC形成整个过程中,COX-2与PI呈正相关(r=0.61,P<0.05)。结论在GC形成过程中,COX-2的表达呈递增趋势;COX-2的表达上调可能是GC形成的早期事件,且其表达水平和PI对评价GC的恶性程度、有无转移和预后有一定参考价值;COX-2在GC形成的不同?

Objective To study the expression of cyclooxygenase-2 (COX-2) in the gastric epithelial carcinogensis and its relation with cell apoptosis and proliferation. Methods 15 cases of normal gastric mucosa (NGM), 30 cases of intestinal metaplasia (IM), 30 cases of dysplasia (Dys) and 40 cases of gastric cancer (GC) were used in this study. The expressions of COX-2 and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemical SABC method, and cell apoptosis was measured by TUNEL. Results The expression level of COX-2 gradually increased from NGM, IM, Dys to GC. The positive rate of COX-2 in GC was 67.5%, 13.3% in NGM, and 33.3% in IM. There was a significant difference in COX-2 expression between GC and IM, GC and NGM(P<0.05). Cell apoptosis index(AI) was 2.8±0.6 in GC. AI in GC was the lowest among all the pathological lesions (P<0.01). Proliferation index (PI) from NGM, IM, Dys to GC also had an increasing tendency, and there were significant differences in PI between GC and the other precancerous lesions (P<0.01). There was no significant difference in COX-2 expression among various precancerous lesions (P>0.05). The expression of COX-2 in poorly differentiated cancer was markedly higher than that in well differentiated cancer (P<0.05). The expression of both COX-2 and PI was closely correlated with the lymph node metastasis and vascular invasion of GC (P<0.05). From NGM to IM, COX-2 expression level was positively correlated with AI (r=0.55,P<0.05), but from Dys to GC, the negative correlation between COX-2 expression level and AI was observed (r=-0.56,P<0.05). During gastric epithelial carcinogenesis, COX-2 expression was positively correlated with PI(r=0.61,P<0.05). Conclusion COX-2 expression gradually increased during gastric epithelial carcinogenesis, and up-regulation of COX-2 may be an early event in this process. The expression level of COX-2 and PI may be helpful for evaluating the malignant degree metastasis and prognosis of GC. At the different stages of gastric carcinogenesis, COX-2 could stimulate cell proliferation, but at the early stages it promoted cell apoptosis, and inhibited cell apoptosis at the late stage.