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ERCC1 表达分析能否有助于鼻咽癌的个体化治疗?

Can the analysis of ERCC1 expression contribute to individualized therapy in nasopharyngeal carcinoma?

机构信息

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong.

出版信息

Int J Radiat Oncol Biol Phys. 2011 Apr 1;79(5):1414-20. doi: 10.1016/j.ijrobp.2009.12.072. Epub 2010 Jun 3.

Abstract

PURPOSE

To analyze the expression of excision repair cross-complementation group 1 (ERCC1) protein in predicting the clinical outcome of nasopharyngeal carcinoma (NPC).

METHODS AND MATERIALS

The histologic specimens of 258 patients with Stage III to IVB nonkeratinizing NPC who were treated with radiotherapy alone (Group I) or concurrent-adjuvant chemoradiotherapy (Group II) were retrieved. Immunostaining on ERCC1 protein was performed. The relationship of ERCC1 expression and clinical outcomes was analyzed.

RESULTS

The median ERCC1 score (proportion score of positively stained cells times intensity) was 200 (range, 0-300), and ERCC1 expression was defined as high if the score was above the median. In Group I high-score tumor had a statistically lower locoregional failure-free rate (LRFFR) compared with low-score tumor (p < 0.05) but not distant failure-free rate (DFFR) and overall survival (OS). In Group II no statistically differences were noted in LRFFR, DFFR and OS with regard to the ERCC1 expression. Resistance to cisplatin-containing chemotherapy in high-ERCC1 score tumor was not observed in Group II. Interestingly, low-score tumor in Group I achieved similar local and distant control compared with Group II. Multivariate analysis showed that ERCC1 score was an independent prognostic factor in LRFFR (p < 0.05) and approached statistical significance in failure-free survival (p = 0.08) and OS (p = 0.07). Tumor with high ERCC1 score had a 2-fold (95% confidence interval, 1.02-3.85) increased risk of locoregional failure. This may imply an association of ERCC1 expression with the repair of radiation damage.

CONCLUSIONS

High ERCC1 expression predicts poor locoregional control in NPC. Chemotherapy response is not affected by ERCC1 expression. Further validation is required.

摘要

目的

分析切除修复交叉互补基因 1(ERCC1)蛋白的表达对预测鼻咽癌(NPC)临床结局的作用。

方法和材料

检索了 258 例接受单纯放疗(I 组)或同期放化疗(II 组)的 III 至 IVB 期非角化性 NPC 患者的组织学标本。进行 ERCC1 蛋白免疫组化染色。分析 ERCC1 表达与临床结果的关系。

结果

ERCC1 评分(阳性染色细胞比例评分乘以强度评分)的中位数为 200(范围 0-300),评分高于中位数则定义为高表达。在 I 组中,高评分肿瘤的局部无复发生存率(LRFFR)显著低于低评分肿瘤(p<0.05),但远处无复发生存率(DFFR)和总生存率(OS)无显著差异。在 II 组中,ERCC1 表达与 LRFFR、DFFR 和 OS 均无显著相关性。在 II 组中,未观察到高 ERCC1 评分肿瘤对含顺铂化疗的耐药性。有趣的是,I 组中低评分肿瘤的局部和远处控制与 II 组相似。多因素分析显示,ERCC1 评分是 LRFFR 的独立预后因素(p<0.05),在无失败生存(p=0.08)和 OS(p=0.07)方面也接近统计学意义。ERCC1 高评分肿瘤的局部区域失败风险增加 2 倍(95%置信区间,1.02-3.85)。这可能提示 ERCC1 表达与放射损伤修复有关。

结论

ERCC1 高表达预测 NPC 局部区域控制不良。ERCC1 表达不影响化疗反应。需要进一步验证。

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