切除的胃腺癌中 ERCC1 和胸苷酸合成酶的差异表达及其预后价值。
Differential expression and prognostic value of ERCC1 and thymidylate synthase in resected gastric adenocarcinoma.
机构信息
Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
出版信息
Cancer. 2013 Sep 1;119(17):3242-50. doi: 10.1002/cncr.28175. Epub 2013 May 29.
BACKGROUND
Excision repair cross-complementing gene-1 (ERCC1) and thymidylate synthase (TS) are key regulatory enzymes whose expression patterns are associated with overall survival (OS) in several malignancies. Their expression patterns and prognostic value in resected gastric adenocarcinoma (GAC) are not known.
METHODS
In total, 109 patients who underwent resection for GAC between January 2000 and June 2011 had tissue available for analysis. The primary objective was to assess for the differential expression of ERCC1 and TS using immunohistochemistry. The secondary objective was to assess for the association between OS and the expression of ERCC1 and TS.
RESULTS
The median follow-up was 21.2 months, and the median OS was 28.8 months. Resected GAC exhibited differential expression of ERCC1 (high expression, 23%; n = 25) and TS (high expression, 43%; n = 47). ERCC1 and TS expression were not associated with OS. In a subset analysis of patients who received chemotherapy (n = 73), high ERCC1 expression was associated with decreased OS (16.7 months vs 53.8 months; P = 0.03). After controlling for known adverse pathologic features, high ERCC1 expression persisted as a negative prognostic factor in multivariate Cox regression analysis (hazard ratio, 2.5; 95% confidence interval, 1.03-6.0; P = .04). Conversely, in patients who underwent resection only (n = 35), high ERCC1 expression demonstrated a trend toward improved OS (40.4 months vs 12.7 months; P = .10); a positive prognostic influence also was present on multivariate analysis (hazard ratio, 0.20; 95% confidence interval, 0.04-0.86; P = .03).
CONCLUSIONS
Resected GAC exhibited differential expression of TS and ERCC1. Among all patients, ERCC1 and TS expression levels were not associated with OS. High ERCC1 tumor expression was associated with decreased OS in the patients who received chemotherapy but was associated with increased OS in those who underwent surgery alone. ERCC1 expression had prognostic value in resected gastric cancer, and further investigation is warranted.
背景
切除修复交叉互补基因 1（ERCC1）和胸苷酸合成酶（TS）是关键的调节酶，其表达模式与多种恶性肿瘤的总生存期（OS）相关。它们在切除的胃腺癌（GAC）中的表达模式和预后价值尚不清楚。
方法
总共对 2000 年 1 月至 2011 年 6 月期间接受 GAC 切除术的 109 名患者进行了组织学分析。主要目的是使用免疫组织化学评估 ERCC1 和 TS 的差异表达。次要目标是评估 ERCC1 和 TS 的表达与 OS 之间的关系。
结果
中位随访时间为 21.2 个月，中位 OS 为 28.8 个月。切除的 GAC 表现出 ERCC1（高表达，23%；n=25）和 TS（高表达，43%；n=47）的差异表达。ERCC1 和 TS 的表达与 OS 无关。在接受化疗的患者亚组分析中（n=73），高 ERCC1 表达与 OS 降低相关（16.7 个月 vs 53.8 个月；P=0.03）。在多变量 Cox 回归分析中，控制已知的不良病理特征后，高 ERCC1 表达仍然是负预后因素（危险比，2.5；95%置信区间，1.03-6.0；P=0.04）。相反，在仅接受切除术的患者中（n=35），高 ERCC1 表达有改善 OS 的趋势（40.4 个月 vs 12.7 个月；P=0.10）；在多变量分析中也存在阳性预后影响（危险比，0.20；95%置信区间，0.04-0.86；P=0.03）。
结论
切除的 GAC 表现出 TS 和 ERCC1 的差异表达。在所有患者中，ERCC1 和 TS 的表达水平与 OS 无关。在接受化疗的患者中，高 ERCC1 肿瘤表达与 OS 降低相关，但在仅接受手术的患者中，高 ERCC1 表达与 OS 增加相关。ERCC1 表达对切除的胃癌有预后价值，需要进一步研究。
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