Kim J-S, Kim M-A, Kim T M, Lee S-H, Kim D-W, Im S-A, Kim T-Y, Kim W H, Yang H-K, Heo D S, Bang Y-J, Lee K-U, Choe K-J, Kim N K
Department of Internal Medicine, Seoul National University Hospital, Republic of Korea.
Br J Cancer. 2009 Mar 10;100(5):732-8. doi: 10.1038/sj.bjc.6604936.
The aim of this study was to analyse the impact of epidermal growth factor receptor (EGFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), aurora kinase (ARK) A/B, and excision repair cross-complementing gene 1 (ERCC1) on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Normal and cancer tissue were separately obtained from gastrectomy samples of 153 patients with AJCC stage III-IV (M0) who subsequently treated with adjuvant FP chemotherapy. TS, DPD, TP, ERCC1, and ARK proteins were measured by immunohistochemistry (IHC). EGFR expression was investigated using a standardized IHC with the EGFR PharmDx assay. Amplification of EGFR gene was analysed using fluorescent in situ hybridisation (FISH). In multivariate analysis, stage, ratio of positive to removed lymph nodes, and EGFR expression were significant prognostic factors for overall survival. Patients with higher EGFR expression had better overall survival than those with lower expression (relative risk: 0.475 (95% confidence interval, 0.282-0.791, P=0.005). Low EGFR expression might be a predictive marker for relapse in curative resected stage III-IV (M0) gastric cancer patients who received adjuvant FP chemotherapy.
本研究旨在分析表皮生长因子受体（EGFR）、胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）、胸苷磷酸化酶（TP）、极光激酶（ARK）A/B和切除修复交叉互补基因1（ERCC1）对根治性胃切除术后5-氟尿嘧啶和顺铂（FP）辅助化疗疗效的影响。从153例AJCC III-IV期（M0）胃癌患者的胃切除标本中分别获取正常组织和癌组织，这些患者随后接受了FP辅助化疗。通过免疫组织化学（IHC）检测TS、DPD、TP、ERCC1和ARK蛋白。使用EGFR PharmDx检测法通过标准化的IHC研究EGFR表达。使用荧光原位杂交（FISH）分析EGFR基因的扩增情况。在多变量分析中，分期、阳性淋巴结与切除淋巴结的比例以及EGFR表达是总生存的显著预后因素。EGFR表达较高的患者总生存情况优于表达较低的患者（相对风险：0.475（95%置信区间，0.282-0.791，P=0.005）。低EGFR表达可能是接受FP辅助化疗的根治性切除III-IV期（M0）胃癌患者复发的预测标志物。
