Clusterin、Livin、Caspase-3蛋白在乳腺浸润性导管癌中的表达

Expression of Clusterin、Livin、Caspase-3 protein in invasive ductal breast cancer

目的:探讨细胞凋亡相关因子Clusterin、Livin、Caspase-3在乳腺浸润性导管癌组织中的表达及临床意义。方法:应用免疫组织化学SP法检测70例乳腺浸润性导管癌、20例乳腺增生和10例乳腺癌旁组织(距癌组织≥4cm,组织学结构正常)标本中Clusterin、Livin、Caspase-3的表达情况,探讨三者的相关性及其与乳腺癌各临床病理学参数间的关系。结果:Clusterin、Livin蛋白在癌组织中的阳性表达率分别为71.4%和64.3%,均明显高于乳腺增生和乳腺癌旁组织的20%、25%(P<0.05)和0%、10%(P<0.05),且Clusterin蛋白与Livin蛋白表达呈正相关(P<0.05)。Caspase-3蛋白在癌组织中的阳性表达率为45.7%,明显低于乳腺增生和乳腺癌旁组织中的75%和80%(P<0.05),且Clusterin、Livin蛋白与Caspase-3蛋白表达呈负相关(P<0.05)。Clusterin蛋白在乳腺浸润性导管癌中的表达随着临床分期的增加阳性表达率显著升高且与组织学分级及淋巴结转移情况有关(P<0.05),与患者年龄、肿瘤大小无关(P>0.05),而Livin蛋白的阳性表达率随着临床分期增加显著升高(P<0.05),但与患者年龄、肿瘤大小、组织学分级、淋巴结转移无关(P>0.05),Caspase-3蛋白的表达随着临床分期的增加其阳性表达率下降(P<0.05),与患者年龄、肿瘤大小、组织学分级和淋巴结转移无相关性(P>0.05)。在乳腺浸润性导管癌组织中Clusterin、Livin蛋白与ER、PR的表达负相关(P<0.05),与C-erbB-2的表达无相关性(P>0.05),Caspase-3蛋白与ER、PR表达显著正相关(P<0.05),与C-erbB-2表达无相关性(P>0.05)。结论:Clusterin、Livin可能通过抑制细胞凋亡在乳腺癌的发生发展中发挥重要促进作用,二者可能成为乳腺浸润性导管癌诊断的重要标志物和评估预后的潜在指标;Clusterin与Livin的联合靶向治疗,有望成为乳腺浸润性导管癌治疗的新方法。Caspase-3在Clusterin、Livin抗凋亡通路中发挥着重要作用。

Objective： To investigate the expression of Clusterin、 Livin、Caspase-3 protein in invasive ductal breast cancer and its clinical significance.Methods： Expression of Clusterin、Livin、Caspase-3 protein in adjacent normal breast tissue that collected from 70 cases of invisive ductal breast cancer,20 cases of breast hyperplasia,as well as 10 cases of breast cancer were evaluated with SP immunohistochemistry（IHC）.The correlation among expression of the Clusterin、Livin、Caspase-3 protein and their relationship with other clinical pathological parameters were investigated.Results： Clusterin、Livin expression in breast cancer tissues were 71.4%、64.3%,significantly higher than 20%、25% in benign lesions and 0%、10% in adjacent normal tissues（P〈0.05）;Expression of Clusterin proteins in breast cancer tissues were positively related to that of Livin proteins（P〈0.05）.The positive expression of Caspase-3 in breast cancer tissues was 45.7%,significant lower than 75% in benign breast lesions,and 80% in adjacent tissues（P〈0.05）.expression of Clusterin、Livin proteins in breast cancer tissues were negatively correlated with that of Caspase-3 protein（P〈0.05）.expression of Clusterin protein expression in ductal breast cancer increased with the histologic grade and was related to lymph node metastasis status（P〈0.05）,but it was irrelevant to the age or tumor size（P〈0.05）;Similarly,expression of Livin protein in ductal breast cancer increased with clinical grade the but no correlation between its expression and age,tumor size,lymph node metastasis status or histologic grade was found（P〈0.05）.Expression level of Caspase-3 protein decreased with clinical stage（P〈0.05）,and was irrelevant to the age,tumor size,histologic grade and lymph node metastasis（P〈0.05）.Clusterin、Livin proteins were negatively related to ER and PR in breast cancer tissues（P〈0.05）,and was not correlated with C-erbB-2 protein（P〈0.05）.Caspase-3 proteins were related to ER and PR in breast cancer tissues（P〈0.05）,but uncorrelated with C-erbB-2 proteins（PD0.05）.Conclusion： Clusterin、Livin may play an important role in the onset and development of breast cancer by inhibiting cell apoptosis,thus can be potential indicator for prognosis of ductal breast cancer.Besides,therapy target to both Clusterin、Livin can be new treatment for ductal breast cancer.This study also suggeste that Caspase-3 protein play an important role in the anti-apoptotic pathway of Clusterin、Livin.