乳腺癌组织中抗凋亡基因survivin、P53和PCNA蛋白的表达及其相关性的探讨

目的 检测乳腺癌组织中生存素(survlvin)、p53和PCNA蛋白的表达,探讨它们对肿瘤凋亡通路调节的机制,进一步了解与凋亡相关的两个蛋白的内在联系。方法 用免疫组织化学法检测40例乳腺癌和15例乳腺良性肿瘤survivin、p53和PCNA蛋白的表达。结果 乳腺癌组织中survivin、p53和PCNA的阳性率分别为90％、37．5％和100％。Survivin的表达在良、恶性乳腺肿瘤间有显著差别(P=0．001)。Survivin基因阳性表达与患者年龄、p53蛋白的表达无相关性(P＞0．05);与肿瘤组织学类型有关,预后好的髓样癌和粘液腺癌阳性程度较低,而预后差的浸润性小叶癌和浸润性导管癌阳性程度较高,两者差异有显著性差别(P＜0．05)。Survivin的表达与PCNA密切相关,表明乳腺癌细胞增殖大于凋亡。结论 抗凋亡基因survlvin和增殖细胞核抗原PC-NA的高表达、p53蛋白的失活抑制了肿瘤的凋亡,也预示着肿瘤的预后不佳。Survivin可能是乳腺癌中一个独立的预后指标。

Surivivin Expression in Breast Carcinoma:Correlation with Apoptotic Markers and Prognosis

Purpose To assess the expression of survivin,p53 and PCNA in breast carcinoma and to discuss the mechanism of apoptotic path-way. Methods 55 cases of formalin-fixed paraffin-embeded malignant and benign breast cancinoma were detected using immunohistochemical method with the monoclonal antibody against survivin,p53 and PCNA. Results Expression of survivin,p53 and PCNA was 90%,37.5% and 100%,respectively.The difference between malignant and benign breast carcinoma was significant (P=0.001).There was no significant correlation between survivin expression and age and p53(P>0.05).There was significant correlation between survivin expression and histologic type.The difference between mucinous,medullary carcinoma and invasive ductal,lobular carcinoma was significant (P<0.05).Survivin expression was strongly associated with PCNA.It suggested that in breast cancinoma,tumor cells were inclined to jproliferation and not apoptosis. Conclusions Over-expression of survivin,PCNA and frequent mutation of p53 may inhibit apoptotic pathway.They may be involved in the development and poor progress of breast carcinoma.The results suggest that apoptosis inhibition by survivin,alone or in cooperation with mutant p53 and PCNA may induce poor outcome in breast carcinoma.