Department of Medical Oncology, Infanta Sofía Hospital, 28702 San Sebastian De Los Reyes, Madrid, Spain.
Int J Oncol. 2012 Jun;40(6):2104-10. doi: 10.3892/ijo.2012.1378. Epub 2012 Feb 16.
Small cell lung cancer is the most aggressive lung cancer subtype. The standard treatment approach is based on cisplatin regimens. Although response rates to treatment are approximately 60-80%, the median survival is still very poor. Excision repair cross complementation group 1 (ERCC1) is an enzyme that removes cisplatin-induced DNA adducts and has been related with prognosis and cisplatin response. Topotecan is the standard treatment as second-line therapy and it is an inhibitor of topoisomerase I (TOP I). We selected 76 patients with small cell lung (SCLC) to analyze the ERCC1 and TOP I mRNA expression. ERCC1 was studied both by quantitative PCR and immunohistochemistry. A significant association was found between the inmunohistochemistry expression of ERCC1 and the lack of platinum response (p=0.001). Moreover, low levels of TOP I RNA were shown to be linked to cisplatin response (p=0.002). In the survival analysis, a significant correlation between a better PFS with a low TOP I RNA expression as well as a negative ERCC1 inmunostaining were found, in both cases with a significant p-value (p=0.02 and 0.009, respectively). In summary, our results suggest the use of ERCC1 immunohistochemistry and TOP I mRNA analysis to predict cisplatin response and prognosis in SCLC patients.
小细胞肺癌是最具侵袭性的肺癌亚型。标准治疗方法基于顺铂方案。尽管治疗的缓解率约为 60-80%，但中位生存期仍然很差。切除修复交叉互补组 1（ERCC1）是一种酶，可去除顺铂引起的 DNA 加合物，并与预后和顺铂反应相关。拓扑替康是二线治疗的标准治疗药物，它是拓扑异构酶 I（TOP I）的抑制剂。我们选择了 76 名小细胞肺癌（SCLC）患者来分析 ERCC1 和 TOP I mRNA 表达。通过定量 PCR 和免疫组织化学研究了 ERCC1。发现 ERCC1 的免疫组织化学表达与缺乏铂类反应之间存在显著相关性（p=0.001）。此外，低水平的 TOP I RNA 与顺铂反应相关（p=0.002）。在生存分析中，发现低水平的 TOP I RNA 表达与 ERCC1 免疫染色阴性与更好的 PFS 之间存在显著相关性，在这两种情况下，p 值均具有统计学意义（p=0.02 和 0.009）。总之，我们的结果表明，使用 ERCC1 免疫组织化学和 TOP I mRNA 分析来预测 SCLC 患者对顺铂的反应和预后。
