原发性乳腺癌组织中端粒酶活性表达与癌细胞凋亡相关性的研究

目的 :探讨原发性乳腺癌组织中端粒酶活性表达与细胞凋亡发生基因表达的相关性及其预后意义。　方法 :应用端粒酶 TRA P- PCR电泳、银染及 EL ISA法、凋亡细胞原位检测 (TU NEL法 )和 S- P免疫组化染色等技术 ,分别对端粒酶定性和定量测定其活性 (TA)、计算凋亡指数 (AI)、检测凋亡相关基因 Bcl- 2和 p5 3蛋白表达水平。　结果 :TA定性检测平均阳性率为 89.8%、定量测定吸光值中位数 0 .6 3± 0 .2 9,均明显高于正常乳腺和良性病变组织(P<0 .0 5 ) ,其表达阳性率高者预后较差 ,5年累积生存率 (6 0 .3% )低于阴性者 (77.4% ) ,二者有显著差异 (P<0 .0 5 ) ,但酶表达与患者年龄、临床 TNM分期、肿瘤大小、发生部位、病理学类型、淋巴结转移等无关。 AI中位数4.83± 0 .74,与 TA表达高度相关 (r=0 .7331,P <0 .0 5 ) ,凋亡相关基因 Bcl- 2和 p5 3蛋白表达阳性率分别为6 3.4%和 40 .7% ,其中 Bcl- 2表达水平与 TA、AI高低呈高度正相关 (r=0 .7814,P<0 .0 5 ) ,p5 3与之呈负相关 (r=- 0 .6 2 5 5 ,P<0 .0 5 ) ;经多变量 Cox回归分析显示仅 TA、AI对乳腺癌患者生存期有影响 ,TA阳性率高、AI>4.0 %者的平均生存时间短于 TA阴性、AI<4.0 %者 (P<0 .0 5 )。此外 ,术前接受化疗者的 TA表达水平低于未化疗者 (6 4.7

Association between the expression of telomerase activity and apoptosis in primary breast cancer patients

Objectives:To investigate the association and the prognostic significance of the expression of telomerase activity (TA) and apoptosis (APO) in tissues of primary breast cancer.Methods:TRAP-PCR and ELISA were developed to detect the expression of TA,and make quantitative and qualitative analysis respectively.TUNEL was also used to evaluate apoptosis cells in cancer lesions and count apoptosis index (AI).The expression levels of proteins of oncogene Bcl-2 and p53 were measured by means of S-P immunohistochemistry.Results:The mean TA positive expression rate was 89.8%,and its mean optic density was (A) 0.63±0.29,which were significantly higher than those of normal tissues and benign breast lesions (P<0.05).The 5 years survival rate of patients with positive TA expression was lower (60.3%) than those of negative expression (77.4%).There were no relations between TA expression and patients ages,TNM staging,lymph nodes metastasis,size,locations and pathological types of cancer.But TA was positively correlated with APO (r=0.733 1,P<0.05) and the protein expression of oncogene Bcl-2 (r=0.781 4,P<0.05) and negatively correlated with that of p53 (r=-0.625 5,P<0.05).Moreover,in patients receiving preoperative chemotherapy,the levels of TA expression were much lower than those without chemotherapy (64.7% vs 85.1%),and the former had higher AI than the latter (7.19±3.75% vs 3.23±2.04%),intraarterial chemotherapy group were superior significantly to adjuvant group (P<0.05).Multivariate Cox Regression Analysis showed that only TA and AI influenced the survival time of primary breast cancer patients,and patients with higher positive TA expression and AI>4.0% had shorter survival time than those of negative TA expression and AI<4.0% patients.Conclusions:There was a significant correlation between TA and APO and its related oncogene Bcl-2,p53.TA and APO are of great diagnostic values,therapeutic helps and prognostic significance in the formation and the development of primary breast cancer.