p53 mRNA及bcl-2、bax蛋白在直肠癌组织中的表达及意义

Expression of p53 mRNA and bcl-2、bax Protein in Rectal Cancer and their Clinical Significance

目的研究p53mRNA及bcl-2、bax蛋白在直肠癌组织中的表达及其意义。方法应用组织芯片技术制作正常直肠、腺瘤组织标本各16例及80例直肠癌石蜡标本的组织芯片,采用原位分子杂交检测p53 mRNA,免疫组织化学SP法检测bcl-2、bax蛋白,脱氧核糖核苷酸末端转移酶介导的缺口末端标记技术(TUNEL)检测直肠癌细胞的凋亡指数。结果正常直肠组织平均p53mRNA阳性细胞率为15.26%±3.24%,腺瘤组织平均阳性细胞率为27.32%±5.54%,直肠癌组织平均阳性细胞率为75.38%±9.61%,三者比较,差异有统计学意义(P<0.01),直肠癌患者不同年龄、性别、肿瘤部位、大小、血清CEA水平、组织学类型的p53表达程度差异无统计学意义(P>0.05);不同分化程度、病理分期、淋巴转移、5年生存率的p53表达程度差异有统计学意义(P<0.05);直肠癌组织bcl-2蛋白表达水平明显高于正常直肠组织和腺瘤(P<0.01),bax蛋白表达水平低于正常直肠组织和腺瘤(P<0.01),直肠癌组织p53mRNA阳性细胞率与bcl-2蛋白表达呈正相关(P<0.01),与bax蛋白表达呈负相关(P<0.01);直肠癌p53mRNA表达程度不同的直肠癌细胞凋亡指数(AI)差异有统计学意义(F=49.85,P<0.01)。结论直肠癌中p53及bcl-2、bax的异常表达共同参与了肿瘤的发生发展和浸润转移,联合检测上述标志物有一定的临床意义。

Objective To investigate the expression and significance of p53 mRNA and bcl-2 ,bax protein in rectal carcinoma with tissue microarray technology. Methods Rectal carcinoma tissue microarray technology was established to detect p53 mRNA and bcl-2 ,bax protein expression in 80 cases of rectal carcinoma, 16 cases rectal adenoma and 16 case of Haemorrhoids （PPH） in the same period of time as the control, p53 mRNA was detected by using in situ hybridization. The expressions of bcl- 2 and bax were determined immunohistochemically, and TUNEL technique was used to detect apoptosis index of rectal cancer cell. The relationships to clinicopathological factors such as differentiation grades and 5-years survival rate were observed. Results The expressions of p53 mRNA and bcl-2 ,bax protein were significantly different in rectal carcinomas in adenoma and normal rectal tissues （ P 〈 0.01 ）. Clinicopathological analysis of patients showed that the increase of p53 mRNA expression were not associated with age, sex and serum CEA levels of the patients and sites, sizes, histological classification, but were associated with differentiation grades, pathological stages, lymph nodes metastases and 5-years survival rate. A positive correlation was observed between p53 mRNA and bcl-2 while negative correlations with bax protein and apoptosis （ P 〈 0.01 ）. Conclusion The different expression of p53 mRNA and bcl-2 ,bax protein in rectal carcinomas play an important role in the pathogenesis ,progression ,invasion, and metastases of the tumor. Determination of p53 ,bcl-2 and bax expression would be helpful for decision making of adjuvant therapy.