Caspase-3、Bcl-2和Bak在胃癌中的表达及意义

The expression and significance of Caspase-3,Bcl-2,Bak in gastric carcinoma

目的 研究Caspase-3、Bcl-2、Bak等凋亡相关基因蛋白在胃癌中的表达，与胃癌临床病理特征和预后的相关性。方法 将100例无术前放化疗史的胃癌手术标本和30例对照组胃粘膜制成组织芯片，取样针直径2．0mm。用免疫组化方法分别检测Caspase-3、Bcl-2、Bak的表达；用原位末端标记法进行细胞凋亡指数检测。对随访14个月～13年的47例作生存分析。结果 获得2个组织芯片蜡块，分别含114和116个位点。Caspase-3在正常粘膜的表达（90％）显著高于胃癌组织（56％）（P〈0．01），其表达与胃癌组织学分化、血管神经侵犯相关（P〈0．05），与淋巴结转移和国际抗癌联盟（UICC）临床分期及预后无关。Bcl-2和Bak在胃癌中的表达分别为42％和47％，表达均与组织学分化相关（P〈0．05），与淋巴结转移、血管神经侵犯、UICC分期及预后无关。结论 Caspase-3、Bcl-2和Bak均参与细胞凋亡调控和胃癌生物学进程，但其表达与胃癌预后无关。UICC分期仍然是胃癌的独立预后指标。

Objective To investigate the expression and significance of Caspase-3, Bel-2,13ak in gastric carcinoma. Methods The gastric cancer tissue microarrays were performed in 100 cases of gastric carcinoma without a history of chemoradiation therapy and 30 gastric tissues of control subjects. The diameter of each specimen on tissue microarrays was 2.0 ram. The expression of Caspase-3 as well as Bcl-2 and Bak was investigated irnmunohistochemically. Tumor cell apoptosis was examined by TUNEL method. The association of these subjects was analyzed. Of 100 cases, 47 cases were fol- lowedup from 14 months to 13 years, in which the prognosis was analyzed. Results Two paraffinembedded gastric cancer tissue microarrays were successfully constructed, including 114 and 116 tissue spots, respectively. Irnmunohistochemical analysis showed that Caspase-3 expression was much higher in normal tissues（90%） than that in carcinoma（56%）（P〈0. 01）. The expression of Caspase-3 was significantly associated with histological grades and invading of vessel and nerve（P〈0.05）, but no distinct difference was found with lymph node involvement and UICC stages. The expression of Bcl-2 （42%） and Bak（47%） was correlated with histological grades of the gastric carecinoma（P〈0.05）, but no distinct difference was found with lymph node involvement, invading of vessel and nerve and UICC stages. Patients with positive Caspase-3 and Bak had higher apoptosis index（AI）. However, Bcl- 2 positive was correlated with a lower AI. In 47 cases with followup data, the expression of Caspase-3, Bcl-2 and Bak was unrelated to prognosis. Conclusion Caspase-3, Bcl-2 and Bak were all involved in the progress and regulation of programmed cell death in gastric carcinoma. But their expression was unrelated with the prognosis. UICC stage is still a useful parameter in predicting prognosis.