Department of General, Visceral and Cancer Surgery, Center for Integrated Oncology (CIO Cologne Bonn), University Hospital of Cologne, Cologne, Germany.
J Gastrointest Surg. 2012 Jan;16(1):26-34; discussion 34. doi: 10.1007/s11605-011-1700-x. Epub 2011 Sep 29.
Neoadjuvant radiochemotherapy (RT/CTx) regimens were primarily designed for treatment of squamous cell carcinoma of the esophagus. Own preliminary results demonstrate that also patients with locally advanced adenocarcinoma of the esophagus may achieve a major response in 30% with a 3-year survival rate of 80%. To identify these patients, ERCC1 (rs11615) gene polymorphisms were analyzed. ERCC1 is a key enzyme of the nucleotide excision and repair (NER) complex to prevent DNA inter- and intra-strand crosslinks.
Genomic DNA from 217 patients with cT3/4 adenocarcinoma of the esophagus was extracted from paraffin-embedded tissues. Of these patients, 153 underwent neoadjuvant RT/CTx (CDDP, 5-FU, 36 Gy). For analysis of ERCC1 single nucleotide polymorphisms (SNPs), allelic discrimination was performed by quantitative real-time PCR. Two allele-specific TaqMan probes in competition were used for amplification of ERCC1 (rs11615). Allelic genotyping was correlated with histomorphologic tumor regression after neoadjuvant RT/CTx and survival. Major response (MaHR) was defined as <10% vital residual tumor cells (VRTC).
Analysis of tumor regression revealed a MaHR in 56/153 (36.6%) patients with a 5-year survival rate (5-YSR) of 74% (p < 0.001). ERCC1 gene polymorphisms for all patients showed the following expression pattern: ERCC1 polymorphism (rs11615) CC: n = 27 (12.4%), TT: n = 98 (45.2%), C/T: n = 92 (42.4%). ERCC1 polymorphism CT was identified as a predictor for response to the neoadjuvant RT/CTx (p < 0.001). The 5-YSR for patients with C/T genotype was 51%. Contrary to this, the 5-YSR for the group of patients with a CC/TT polymorphism decreased to 34%.
Analysis of ERCC1 (rs11615) gene polymorphisms reveals a significant correlation with response and survival in patients with adenocarcinoma of the esophagus treated with a neoadjuvant radiochemotherapy. Single nucleotide polymorphisms of ERCC1 (rs11615) could therefore be applied to further individualize therapy in esophageal cancer.
新辅助放化疗（RT/CTx）方案主要用于治疗食管鳞癌。我们的初步结果表明，对于局部晚期食管腺癌患者，30%的患者可能会获得主要缓解，3 年生存率为 80%。为了识别这些患者，我们分析了 ERCC1（rs11615）基因多态性。ERCC1 是核苷酸切除修复（NER）复合物的关键酶，可防止 DNA 链间和链内交联。
从 217 例石蜡包埋组织中提取了 cT3/4 期食管腺癌患者的基因组 DNA。其中 153 例行新辅助 RT/CTx（CDDP、5-FU、36Gy）。为了分析 ERCC1 单核苷酸多态性（SNP），通过实时定量 PCR 进行等位基因鉴别。使用两个等位基因特异性 TaqMan 探针进行 ERCC1（rs11615）的扩增。等位基因基因分型与新辅助 RT/CTx 后组织形态学肿瘤消退和生存相关。主要缓解（MaHR）定义为<10%的存活肿瘤细胞（VRTC）。
肿瘤消退分析显示，153 例患者中有 56 例（36.6%）获得 MaHR，5 年生存率（5-YSR）为 74%（p<0.001）。所有患者的 ERCC1 基因多态性均表现出以下表达模式：ERCC1 多态性（rs11615）CC：n=27（12.4%），TT：n=98（45.2%），C/T：n=92（42.4%）。ERCC1 多态性 CT 被确定为新辅助 RT/CTx 反应的预测因子（p<0.001）。C/T 基因型患者的 5-YSR 为 51%。与此相反，CC/TT 多态性组患者的 5-YSR 降至 34%。
分析 ERCC1（rs11615）基因多态性与接受新辅助放化疗的食管腺癌患者的反应和生存具有显著相关性。ERCC1（rs11615）单核苷酸多态性可进一步应用于食管癌的个体化治疗。
