DNA切除修复交叉互补基因1蛋白的表达与鼻咽癌同步放化疗疗效的关系

 目的　研究DNA切除修复交叉互补基因1（ERCC1）在鼻咽癌中的表达，分析其与鼻咽癌同步放化疗疗效的关系。方法　对鼻咽部肿物活组织检查确诊为非分化型非角化性鼻咽癌患者，接受顺铂（DDP）单药同步放化疗，应用免疫组织化学法检测鼻咽部癌组织中ERCC1蛋白表达。患者同步放化疗结束后8周复查鼻咽部磁共振成像（MRI）以评价其近期治疗敏感性，完全缓解（CR）+部分缓解（PR）评价为治疗敏感组，稳定（SD）+进展（PD）评价为治疗不敏感组，以后每3个月复查1次鼻咽部MRI了解有无复发，随访观察3年疗效。分析ERCC1蛋白表达与同步放化疗近期治疗敏感性及远期生存率的关系。结果　全组76例患者均可评价近期治疗敏感性，72例可评价无疾病进展生存时间及总生存（OS）率。可评价近期治疗敏感性的76例患者中CR为56例（73.68 %），PR 11 例（14.47 %），SD 3 例（3.95 %），PD 6 例（7.89 %）；有效率（RR）88.16 %（67／76），疾病控制率（DCR）92.1 %（70／76）。ERCC1阳性率42.1 %（32／76），其中治疗敏感组中阳性率37.3 %（24／67），不敏感组中阳性率 88.8 %（8 ／9）。ERCC1阴性表达组中有效率（RR）97.7 %（43／44），DCR 97.7 %（43／44），ERCC1阳性表达组 RR 75 %（24／32），DCR 81.3 %（26／32）。ERCC1阴性组的治疗有效率显著高于ERCC1阳性组，其差异有统计学意义（χ2＝7.119，P＜0.05）。72例患者12个月无疾病进展率为91.7 %（66／72）。其中ERCC1阴性组95.5 %（39／41），ERCC1阳性组87.1 %（27／31），两组间无疾病进展率的差异无统计学意义（χ2＝0.623，P＝0.430）。31例ERCC1阳性患者的1、2、3年生存率分别为90.6 %（28／31）、77.4 %（27／31）、61.3 %（19／31）。41例ERCC1阴性患者的1、2、3年生存率分别为95.5 %（39／41）、90.2 %（37／41）、82.9 %（34／41）。两组间生存率的差异有统计学意义（χ2＝4.192，P＝0.041）。结论　鼻咽癌中ERCC1蛋白的表达与同步放化疗近期治疗敏感性呈负相关性，ERCC1的表达可能预测NPC同步放化疗近期治疗敏感性。鼻咽癌的ERCC1蛋白的表达与 OS 呈负相关性，其可能作为判断NPC预后的一项指标。

Relationship between expression of ERCC1 and concurrent chemo-radiotherapy in patients with nasopharyngeal cancer

Objective To detect the ERCC1 expression in nasopharyngeal cancer（NPC）, to analyze its relationship with concurrent chemo-radiotherapy. Methods The biopsy specimens were obtained through nasopharyngeal endoscopy from patients with NPC in the Fourth Affiliated Hospital of Guangxi Medical University from January 2008 to December 2008. The ERCC1 expression in the cancer tissue was detected using MaxVision immunohistochemistry. Eight weeks after the chemo-radiotherapy, MRI was performed, The MRI results were used to assess the efficacy according to RECIST 1.1 standard, with sensitive group including complete relief （CR） and partial relief （PR） and insensitive group including stable disease（ SD ） and progress disease （PD）, MRI was re-performed every three months with follow-up 3 years. The relationships between ERCC1 expression and concurrent chemo-radiotherapy in the short-term sensitivity and overall survival in patients with nasopharyngeal cancer were analyzed. Results 76 cases were collected. All cases were evaluable for the short-term sensitivity, and only 72 cases were evaluable for progression-free rate and overall survival （OS）. In 76 short-term curative effect evaluable cases, CR was 56 cases （73.68 %）, PR was 11 cases （14.47 %）, SD was 3 cases （3.95 %）, PD was 6 cases （7.89 %）, respectively. RR （effective efficiency） was 88.16 % and DCR （disease control rate） was 92.1%. The positive rate of ERCC1 expression was 42.1% （32/76）, with 37.3 % （24/67） in the sensitive group （CR＋PR） and 88.8 % （8/9） in the non-sensitive group （SD＋PD）. RR and DCR in the negative ERCC 1 expression group were higher （97.7 %, 97.7 %） than those in the positive expression group （75 %, 81.3 %, χ^2 = 7.119, P 〈 0.05）. Of 72 case, twelve month progression-free survival （PFS） rate was 91.7 % （66/72）, with 95.5 % （39/41） in the negative ERCC1 expression group and 87.1% （27/ 31） in the ERCC 1 positive group, and there was no significant difference between the 2 groups （X 2 = 0.623, P = 0.430）. Of 72 cases, one year OS rate was 93.0 % （67/72）, two years OS rate was 84.7 % （61/72）, three years OS rate was 72.2 %（52/72）. Of 31 ERCC1 positive cases one year OS rate was 90.6 %（28/31）, two years OS rate was 77.4 % （27/31）, and three years OS rate was 61.3 % （19/31）. Of 41 ERCC1 negative cases one year OS rate was 95.5 %（39/41）, two years OS rate was 90.2 % （37/41）, and three years OS rate was 82.9 % （34/41）. The ERCC1 expression demonstrated significant correlation with the short-term sensitivity and OS （χ^2 = 4.192, P = 0.041）. Conclusion The ERCC1 expression in NPC has negative correlation with the chemo-radiotherapy and short-term sensitivity, which may predict the chemo-radio therapy sensitivity in NPC. The ERCC1 expression in NPC has significant correlation with OS. It may predict the prognosis of NPC.