恶性间皮瘤细胞凋亡与凋亡调节蛋白Bax及Bcl-2表达的关系

Apoptosis of malignant mesothelioma cells and the expression of apoptosis regulating proteins Bcl-2 and Bax

目的研究恶性间皮瘤组织中Bcl-2、Bax表达,肿瘤细胞自发凋亡率（AI）与患者生存时间之间的关系。方法选取79例恶性间皮瘤标本,采用免疫组织化学方法检测肿瘤细胞中Bcl-2、Bax的表达。采用脱氧核糖核苷酸转移酶介导的缺口末端原位标记法（TUNEL）检测肿瘤细胞的自发凋亡率。结果79例中,女性患者32例,男性47例。发病年龄11-79岁,发病高峰年龄40-50岁。患者生存时间5-160个月。根据组织学亚型分类：上皮细胞型51例,肉瘤样型20例,混合型8例。肿瘤细胞自发凋亡率（AI）为0.14-6.9%,高凋亡指数组的生存时间明显短于低凋亡指数组（P〈0.01）。另外,Bcl-2阴性表达组的凋亡指数（AI=1.92）大大高于Bcl-2阳性组的凋亡指数（AI=0.82,r=0.288 0,P=0.01）,说明Bcl-2的表达与肿瘤细胞凋亡之间存在联系。但是凋亡指数与另外一种凋亡调节蛋白Bax之间无显著联系（r=0.0770,P=0.46）。Bcl-2和Bax两种凋亡调节蛋白表达情况对恶性间皮瘤患者的生存时间没有显著性影响（分别为r=0.077 3,P=0.43;r=0.145 7,P=0.26）。结论恶性间皮瘤细胞凋亡指数可以作为判断其预后的重要指标,Bcl-2的表达与肿瘤细胞的凋亡有相关性。

Objective To investigate the expression of apoptosis regulating protein Bol-2 and Bax, and the spontaneous apoptotic index （AI） in malignant mesothelioma, and their relationship to the survival time of patients. Methods Hematoxylin-eosin and immunohistochemical stainings were used for the sections of paraffin embedded tissues of 79 specimens of malignant mesothelioma. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） was used to identify the apoptotic tumor cells. Results The age of the patients with malignant mesothelioma ranged from 11 to 79 years. The peak incidence of malignant mesothelioma was at the age of 40 -50 years. The ratio of male to female was 1. 47：1. The survival time of the 79 cases was between 5 and 160 months, and the medial survival time was 23 months. According to histological pictures, these tumors were diagnosed as epithelioid type （51 cases）, mixed type （8 cases） and sareomatous type （20 cases）. The tumor spontaneous apoptotic index （AI） was 0. 14%-6.9%. The survival time of the patients with higher AI was significantly shorter than those with lower AI （P〈0. 01）. In addition, the AI of the eases with Bob2 negative expression was 1.92, remarkably higher than those cases with Bob2 positive expression （AI=0. 82, r=0. 288 0, P=0. 01）. The results showed that Bcl-2 expression was associated with the apoptotic index. However, the apoptotic index did not significantly associate with the Bax expression （r=0. 077 0, P=0. 46）. The level of both Bcl-2 and Bax expression had no significant effect to the survival of the patients with malignant mesothelioma （ r= 0. 077 3, P= 0. 43 and r= 0. 145 7, P= 0. 26, respectively）. Conclusion The apoptotic index may act as an indicator of the prognosis of the patients with malignant mesothelioma. The expression of Bol-2 is associated with the apoptosis in malignant mesothelioma.