Bax and Bcl-2 expression predict response to radiotherapy in advanced cervical cancer

目的：Bcl2/Bax表达的比值决定了细胞凋亡刺激后的生存或死亡。为了建立一个新的预测宫颈癌治疗结果的指标，我们研究了10.8GY治疗后Bax和Bcl2蛋白的表达与放疗疗效的关系。方法：44例经组织学证实的宫颈癌患者，包括3例复发的宫颈残端癌患者，接受了确定性放射治疗。用单链构象多态分析和DNA测序分析P53基因第5-8外显子的突变情况。结果：40例患者为野生型P53，4例为突变型P53。放疗前Bax和Bcl2蛋白的表达与疗效或生存期无关。而放疗后Bax和Bcl2蛋白的表达与疗效或生存期均相关。Bax阳性肿瘤对10.8Gy射线照射的疗效明显好于Bax阴性肿瘤(P=0.0002)。Bcl2阳性肿瘤放射治疗反应明显低于Bcl2阴性肿瘤(P=0.002)。10.8Gy放疗后Bax蛋白表达增加与患者的生存状况相关(P=0.04)。结论：宫颈癌放疗后Bax和Bcl2表达水平可作为判断预后的有用指标。

Purpose : The ratio of Bcl-2 to Bax expression determines survival or death following an apoptotic stimulus. In order to establish a new predictor of the outcome of treatment for human cervical carcinoma, we investigated the relationship between the expressions of the Bax and Bcl-2 proteins and the response to radiotherapy after the administration of 10.8 Gy.Methods : A total of 44 patients with histologically proven carcinoma of the uterine cervix, including three with recurrent cervical stump carcinomas, were treated with definitive radiotherapy. The presence of mutations in exons 5-8 of the p53 gene was analyzed by a single-strand conformation polymorphism analysis and DNA sequencing.Results : Forty patients were found to have wild-type p53, and the remaining four had mutant p53. The Bax and Bcl-2 protein expressions prior to radiotherapy did not correlate with response or survival. However, the Bax and Bcl-2 protein expressions after radiotherapy correlated with both response or survival. Bax-positive tumors showed significantly better responses than the Bax-negative tumors after 10.8 Gy radiation (P=0.0002). In contrast, the Bcl-2-positive tumors showed significantly poorer responses than the Bcl-2-negative tumors after radiation (P=0.002). Increased Bax expression after the 10.8 Gy radiotherapy was found to be correlated with good survival (P=0.04). In contrast, increased Bcl-2 expression after such radiotherapy was correlated with poor survival (P=0.002).Conclusion : The levels of Bax and Bcl-2 expression after 10.8 Gy of radiotherapy are useful prognostic markers in patients with human cervical carcinoma.