细胞凋亡及其相关基因与乳腺癌预后关系的研究

Study on the Relationship between Apoptosis and Its Related Genes and the Porgnosis of Breast Cancer

目的 :分析乳腺癌中凋亡细胞数量、凋亡相关基因—bcl 2、p5 3的表达、细胞增殖标志物PCNA(增殖细胞核抗原 )的表达 ,与影响乳腺癌预后的因素 (肿瘤大小 ,TNM分期 ,淋巴结转移情况 ,雌孕激素受体情况等 )之间的关系及其对预后的影响。方法 :凋亡细胞的检测采用原位DNA缺口末端标记TUNEL法 ,bcl 2、p5 3、PCNA、ER(雌激素受体 )及PR(孕激素受体 )检测采用免疫组化LSAB法。结果 :本组 2 0 0例乳腺癌中 ,bcl 2阳性率为 5 1% ,bcl 2高表达及ER、PR阳性 ,肿瘤体积小 ,肿瘤增殖活性低 ,p5 3阴性 ,与ER、PR阴性 ,肿瘤体积大 ,肿瘤增殖活性高及 p5 3阳性者相比 ,差异具有显著性 (P <0 .0 1)。bcl 2高表达者无瘤生存率及总生存率均明显高于bcl 2低表达者。差异具有显著性 (P <0 .0 0 1)。本组乳腺癌的平均AI为 1.89% (范围 0～ 14.8% )。PI为 18.37%± 7.5 1% ,通过相关性分析显示 ,AI与PI呈显著性正相关 ,(r =0 .89,P <0 .0 0 1)。结论 :本研究显示 ,在乳腺癌组织中 ,bcl 2表达抑制bcl 2表达抑制凋亡的发生 ,突变型 p5 3蛋白的表达抑制bcl 2的表达 ,调亡率随增殖率的增加而增加 ,bcl 2高表达、凋亡率低的乳腺癌患者其预后多好于bcl 2低表达而凋亡率高者。

Objective: To study the impact of apoptosis and its related genes on the prognosis of patients with breast cancer.Methods: By using LSAB immunohistochemical technic the expresssion of p53, bcl-2, PCNA and ER-PR were determined in 200 cases of breast cancer. Meanwhile the apoptotic cells in 50 cases were studied with TUNEL technic.Results: The overall positive rate of bcl-2 expression was 51%. The high expression of bcl-2 coincided with those good prognostic factors such as the presence of ER and PR, small tumor size, low activity of proliferation rate and absence of p53 ( P <0.01). The disease-free survival and overall survival of patients with expression of bcl-2 were significantly longer than those without bcl-2 ( P <0.001). The average index of apoptosis (AI) was 1.89%. AI was associated with those poor factors of prognosis such as absence of ER and PR and high proliferation rate etc ( P <0.01). The average index of PCNA (PI) was 18.37±7.51%, and was closely related with AI(r=0.89, P <0.001).Conclusion: In breast cancer, the bcl-2 expression inhibits cellular apoptosis, the expression of p53 down regulates the expression of bcl-2 and AI is closely associated with PI. Therefore, high expression of bcl-2 and low PI are the good prognostic factors of breast cancer.