Survivin和Caspase-3在人类大肠腺瘤及大肠癌中的表达以及与凋亡的关系

Expression of Survivin and Caspase-3 and its relationship to apoptosis in adenoma and carcinoma of human large bowl

目的评价大肠腺瘤及大肠癌组织中Survivin和Caspase-3的表达情况以及与细胞凋亡的关系。方法采用免疫组化二步法,对48例无术前放、化疗史的大肠癌患者的手术标本,20例正常大肠黏膜和25例腺瘤标本,进行Survivin和Caspase-3检测,并用TUNEL法检测凋亡细胞。结果Survivin在正常大肠黏膜中无表达,在管状腺瘤、绒毛状和混合型腺瘤及腺癌中的阳性表达分别为10%、33.3%、70.8%。Caspase-3在正常粘膜、管状腺瘤、绒毛状和混合型腺瘤及腺癌中的阳性表达分别为95%、60%、53.3%、45.8%。正常黏膜组织Caspase-3的表达高于大肠腺瘤和大肠癌(P<0.05)。Survivin和Caspase-3在大肠癌中的表达强度随组织分化程度增高而增强;而在不同的Dukes分期间无显著差异(P>0.05)。大肠癌组织中Survivin与Caspase-3的表达无直线相关关系,Survivin阳性组凋亡指数明显低于阴性组(P<0.005)。结论Survivin在大肠癌发生早期过程中表达上调,有望成为大肠癌新的早期诊断标志物。Survivin作为凋亡抑制蛋白显著抑制癌组织的细胞凋亡,但不能完全抑制Caspase-3的表达。

Objective To evalmate the expression of survivin and caspase-3 in adenoma and carcinoma of human large bowl, and its association with tumor cell apoptosis.Methods The expression of survivin and caspase-3 was investigated immunohistochemically in 48 colorectal carcinoma patients without the history of radio active or chemical therapy,20 cases of normal mucoss and 25 eases of colorectal adenoma.Apoptotic cells were detected by IUNEL method.Results Survivin was not expressed in normal mucoss,the positive expression of survivin in tubular adenoma was 10%, in villous adenoma or tubulovillous adenoma was 33.3%, in colorectal carcinoma was 70.8% .The positive expression of caspase-3 in normal mueosa was 95%, in tubular adenoma was 60% ,in villous adenoma or tubulovillous adenoma was 53.3 %, in colorectal carcinoma was 45.8%, easpase-3 was expressed more obviously in normal tissues than in adenoma and carcinoma tissues. Both of the expression of survivin and caspase-3 had significant differences among different histological grades, but both of them were not associated with different Dukes stages. The expression of survivin in carcinoma was not directly related to that of caspase-3. Patients withsurvivin（ ＋ ） apoptasis index was lower than survivin（ - ）. Conclusion These results show that survivin plays an important role in the early development of colorectal cancer and it may become a potential early diagnostic marker. As an apoptosis inhibitor, survivin obviously inhibited the apoptasis of tumor cells, but couldnot comphtdy inhibit the expression of caspase-3.