Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ann Surg Oncol. 2011 Apr;18(4):1204-11. doi: 10.1245/s10434-010-1414-4. Epub 2010 Nov 13.
Excision repair cross-complementation group 1 (ERCC1) is one of the key enzymes in DNA repair. This study was designed to investigate the correlation between ERCC1 expression and chemosensitivity to cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC).
Eighty-seven HCC samples were analyzed by immunohistochemistry for ERCC1 and chemosensitivity was assessed by the succinate dehydrogenase inhibition (SDI) test for four anti-cancer agents, including CDDP. The ERCC1 expression was examined in HCC cell lines. ERCC1 siRNA was transfected to PLC/RPF/5 to investigate the correlation of ERCC1 expression and CDDP sensitivity.
ERCC1 expression was observed in 33% of nuclei in immunohistochemical examination. Patients were divided into two groups as follows: ERCC1 high expression group (n = 43): more than 33% of the nuclei were stained; ERCC1 low expression group (n = 44): 33% or fewer of the nuclei were stained. Tumor size of low expression group was larger than that in the high expression group (p = 0.02). The succinic dehydrogenase (SD) activity only for CDDP was significantly higher in the high expression group than that in the low expression group (p = 0.02). An increased expression of ERCC1 was shown by immunohistochemical and Western blot analyses in PLC/RPF/5. ERCC1 expression was inhibited by ERCC1 siRNA transfection and the LC50 value (nM) of CDDP was reduced from 25.7 to 12.5 (p = 0.01).
Increased ERCC1 expression is associated with CDDP resistance in HCC specimens and cell lines. Therefore, immunohistochemical analysis for resected HCC tissues may be a useful predictor for the effectiveness of adjuvant chemotherapy, using CDDP.
切除修复交叉互补基因 1（ERCC1）是 DNA 修复的关键酶之一。本研究旨在探讨 ERCC1 表达与肝癌（HCC）患者对顺铂（CDDP）化疗敏感性的相关性。
采用免疫组织化学法检测 87 例 HCC 标本中 ERCC1 的表达，并采用琥珀酸脱氢酶抑制（SDI）试验评估四种抗癌药物（包括 CDDP）的化疗敏感性。检测 HCC 细胞系中 ERCC1 的表达，并转染 ERCC1 siRNA 至 PLC/RPF/5 细胞，以探讨 ERCC1 表达与 CDDP 敏感性的相关性。
免疫组化检查显示 ERCC1 表达在 33%的细胞核中。将患者分为两组：ERCC1 高表达组（n=43）：有超过 33%的细胞核染色；ERCC1 低表达组（n=44）：有 33%或更少的细胞核染色。低表达组的肿瘤大小大于高表达组（p=0.02）。高表达组的顺丁烯二酸脱氢酶（SD）活性仅对 CDDP 显著高于低表达组（p=0.02）。PLC/RPF/5 细胞的免疫组化和 Western blot 分析显示 ERCC1 表达增加。ERCC1 siRNA 转染抑制 ERCC1 表达，CDDP 的 LC50 值（nM）从 25.7 降至 12.5（p=0.01）。
在 HCC 标本和细胞系中，ERCC1 表达增加与 CDDP 耐药相关。因此，对切除的 HCC 组织进行免疫组化分析可能有助于预测使用 CDDP 进行辅助化疗的疗效。
