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背景与目的:细胞凋亡调控失衡在肿瘤发生发展中具有重要意义。Survivin、Caspase3是细胞凋亡和细胞周期调控的重要成员。本研究应用组织芯片技术分析胃癌组织Survivin、Caspase3等的表达与胃癌临床病理特征和生物学预后的相关性及意义。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2.0 mm。用免疫组化方法分别检测Survivin、Caspase3等的表达,用TUNEL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:共获得2个组织芯片蜡块,分别含114和116个位点。组织芯片中,Survivin主要在胃癌中表达(78%),而对照组胃粘膜几乎无表达(P<0.01),Survivin阳性率与胃癌组织学分化、淋巴结转移、血管/神经侵犯(BV/N)及TNM分期相关(P<0.05);Caspase3在正常粘膜的表达(90%)显著高于胃癌组织(56%)(P<0.01),阳性率与胃癌组织学分化、BV/N相关(P<0.05),而与淋巴结转移和TNM分期无关(P>0.05)。Survivin阳性组细胞凋亡指数明显低于阴性组(P<0.01),而Caspase3阳性组凋亡指数明显高于Caspase3阴性组(P<0.05)。在有随访的47例中,单因素Cox分析显示,BV/N、TNM分期及Survivin表达均与预后相关,而组织学分化、Caspase3表达与预后无关,经多因素Cox分析显示,只有TNM分期、Survivin表达具有独立的预后意义。结论:Survivin表达与胃癌临床病理特征及预后密切相关,似可作为胃癌预后差的指标,Caspase3可能参与细胞凋亡调控和胃癌生物学进程。
Background and Aim: The imbalance of apoptosis regulation plays an important role in tumor development. Survivin and Caspase3 are important members of apoptosis and cell cycle regulation. In this study, the relationship between the expression of Survivin and Caspase3 and the clinicopathological features and prognosis of gastric cancer was analyzed by tissue microarray. Methods: 100 gastric cancer specimens without history of preoperative radiotherapy and chemotherapy and 30 normal gastric mucosa were made into tissue microarray. The diameter of the sampling needle was 2.0 mm. The expressions of Survivin and Caspase3 were detected by immunohistochemistry. The apoptotic index was detected by TUNEL method. Survival analysis was performed on 47 cases who were followed up for 14 months to 13 years. Results: Two tissue chip wax blocks were obtained, containing 114 and 116 loci, respectively. Survivin was mainly expressed in gastric cancer (78%), while gastric mucosa was almost not expressed in the control group (P <0.01). Survivin positive rate was correlated with histological differentiation, lymph node metastasis, BV / N, (P0.05). Caspase3 expression in normal mucosa (90%) was significantly higher than that in gastric cancer (56%) (P <0.01). The positive rate of Caspase3 correlated with histological differentiation and BV / N in gastric cancer (P < 0.05), but not lymph node metastasis and TNM stage (P> 0.05). The apoptosis index of Survivin positive group was significantly lower than that of negative group (P <0.01), while the apoptosis index of Caspase3 positive group was significantly higher than that of Caspase3 negative group (P <0.05). Among 47 follow-up cases, univariate Cox analysis showed that BV / N, TNM staging and Survivin expression correlated with prognosis, while histological differentiation and Caspase3 expression had no relationship with prognosis. Multivariate Cox analysis showed that only TNM staging, Survivin expression has independent prognostic significance. Conclusion: The expression of Survivin is closely related to the clinicopathological characteristics and prognosis of gastric cancer, which may serve as a marker of poor prognosis of gastric cancer. Caspase3 may be involved in the regulation of apoptosis and the biological process of gastric cancer.