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

关键词:  DNA-PK  P53  宫颈癌  放射治疗  免疫组织化学

Key words:  DNA-PK  P53  cervical cancer  radiotherapy  immunohistochemistry

摘要:

［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DT1400cGy/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（χ²=36.444，P<0.001）；DNA-PKcs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（χ2=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。

Abstract:

［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 (χ²=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 (χ2=7.483，P<0.001).Moreover, significantly positive correlation between P53 and DNA-PKcs was also found. (r=0.276, P< 0.05, bilateral).［Conclusions］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.