DNA-PKcs、P53的表达与宫颈癌放疗敏感性及预后的关系

Correlationof DNA-PKcs/P53 with radiosensitivity and prognoses of cervical cancer

[目的]研究DNA-PKcs、P53的表达与宫颈癌放疗敏感性及预后的关系。[方法]Ⅰb-Ⅱb期宫颈癌患者63例,术前放疗DT1400 cGy/2次,14 d后行根治术,据术后病理放疗反应分为放疗敏感与放射抗拒两组;免疫组化S-P法检测DNA-PKcs、P53蛋白在治疗前宫颈癌组织中的表达;分析两组表达差异有无显著性意义,二因子有无相关性,及其与生存期的关系。[结果]DNA-PKcs在正常宫颈鳞状上皮、腺上皮中不表达,在癌细胞核中的阳性表达率10%～100%,中位数70%,均数66.67%（标准误2.94%）。DNA-PKcs在放疗敏感组32例中有7例高表达,放射抗拒组31例中有30例高表达（χ^2=36.444,P〈0.001）;DNA-P Kcs高表达组总生存时间均数51月,低表达组59月。P53在癌细 胞核中的表达率0～35%,中位数0,均 数8.49%（标准误1.57%）。P53在放疗敏感组32例中有6 例高表达,放射抗拒组31例中有16例高表达（χ^2=7.483,P〈0.001）;DNA-PKcs与P53相关系数r= 0.276（P〈0.05双侧）。[结论]DNA-PKcs、P53可作为早期宫颈癌放疗敏感性的预测指标,高表达者易放射抗拒;DNA-PKcs与P53表达正相关;DNA-PKcs低表达者预后较好。

[Objective] To investigate theassociation of tumor response to radiotherapy and survival with theexpression of DNA-PKcs and P53.[Methods] Sixty-three patients,pathologically diagnosed cervical cancer,FIGO-stageⅠb-Ⅱb,treated with preoperative brachytherapy,DT1400cGy/2f/14 d,followed by radical surgery,were divided into two groups according to pathological tumor response to radiation-radioresistant or radiosensitive.Formalin-fixed primary uterine cervicaltumor biopsies were investigatedby immunohistochemistry.Expression of P53 and DNA-PKcs in primary tumors was compared and analyzed between the two groups.Correlation between P53 and DNA-PKcs was studied.Survival analysis was also performed.[Results] Tumor-transformed tissue showed positive immunostaining of DNA-PKcs while non-neoplastic squamous epithelium and tumor-free cervix glands showed negative immunoreactivity.The percentage of nuclear-staining-positive cells varied between 10% and 100%,with a median of 70%,（mean：66.67%＋/-2.94%）.It was found that 7 of 32 cases to be DNA-PKcs-high-express in the radiosensitive group,while 30 of 31 in the radioresistant one.DNA-PKcs-high-express tumors showed significantly much radioresistant than DNA-PKcs-low-expressones（χ^2=36.444,P〈0.001） and the latter has a significantly better overall survival（59 months vs 51 months）.The percentage of P53-positive cells varied between 0 and 35%,with a median of 0（mean：8.49%＋/-1.57%）.P53-high-expresswas found in 6 of 32 cases in the radiosensitive group,while 16 of 31 in the radioresistant one.Positive P53 tumors were significantly more common in the radioresistant group（χ^2=7.483,P〈0.001）.Moreover,significantly positive correlation between P53 and DNA-PKcs was also found.（r=0.276,P〈0.05,bilateral）.[Conclusion]DNA-PKcs and P53 couldbe used as predictive markers for radiotherapy response in cervical cancer,high expression of DNA-PKcs and P53 leads to radioresistance;And the two facters have positive correlation;In addition,overall survival issignificantly better in the DNA-PKcs-low-express patients as compared with DNA-PKcs-high-expressones.