Evaluation of ERCC1 Expression for Cisplatin Sensitivity in Human Hepatocellular Carcinoma

Abstract

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.