Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma
Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma
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DOI：
10.3892/or_00000721
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发表时间：
2010-04-01
期刊：
影响因子：
4.2
通讯作者：
Ajioka, Yoichi
中科院分区：
文献类型：
--
作者：
Korita, Pavel V.;Wakai, Toshifumi;Ajioka, Yoichi
我们假设多药耐药相关蛋白2（MRP 2），一种主要的顺铂转运蛋白的表达，可能决定顺铂作为肝细胞癌（HCC）患者治疗的疗效。对49例接受HCC切除术的连续患者进行了前瞻性分析（16例接受基于顺铂的新辅助化疗的患者和33例未接受新辅助化疗的患者）。采用免疫组化和Western blot方法检测MRP 2的表达。肿瘤的程度进行了评估，在组织学上的最大尺寸的肿瘤标本从每个病人。肿瘤坏死百分比中位数为81%（范围：0-100%），3例患者发现肿瘤完全坏死。在24/46（52%）的肿瘤标本中检测到MRP 2的过度表达。16例MRP 2过表达的患者中，顺铂剂量与肿瘤坏死无相关性（P=0.706和P=0.555）。在13例肿瘤标本中，16例顺铂治疗的患者有活体肿瘤。8例MRP 2过表达。MRP 2过表达的肿瘤标本显示肿瘤坏死百分比低于非过表达的肿瘤标本（肿瘤坏死百分比中位数）。19% vs. 99%，P=0.003）。总之，在接受以顺铂为基础的新辅助化疗治疗的HCC患者中，MRP 2的过度表达与较低的肿瘤坏死百分比相关，而肿瘤大小或顺铂剂量均不相关。MRP 2的表达决定了以顺铂为基础的化疗方案在HCC患者中的疗效。
We hypothesized that expression Of multidrug resistance-associated protein 2 (MRP2), a major cisplatin transporter, may determine the efficacy of cisplatin as a treatment for patients with hepatocellular carcinoma (HCC). A prospective analysis was conducted of 49 consecutive patients Who underwent resection for HCC (16 patients treated with cisplatin-based neoadjuvant chemotherapy and 33 patients treated without neoadjuvant chemotherapy). Expression of MRP2 in resected specimens was assessed by immunohistochemical and Western blot analyses. The extent of tumor was assessed histologically in the greatest dimension of the tumor specimen from each patient. The median percentage of tumor necrosis was 81% (range: 0-100%) and complete tumor necrosis was found in 3 patients. Over-expression of MRP2 was detected in 24/46 (52%) tumor specimens. In 16 patients treated with overexpression of MRP2 and dose of cisplatin did not correlate With tumor necrosis Of the resected specimens (P=0.706 and P=0.555, respectively). Of 13 tumor specimens containing, vivid tumor from 16 patients treated with cisplatin. 8 had overexpression of MRP2. Tumor specimens with overexpression of MRP2 showed a lower percentage of tumor necrosis than those with non-overexpression (median percentage of tumor necrosis. 19% vs. 99%, P=0.003). In conclusion, overexpression of MRP2 con-elates with I lower percentage of tumor necrosis in patients treated with cisplatin-based neoadjuvant chemotherapy for HCC, whereas either tumor size or dose of cisplatin does not. Exprexssion of MRP2 determines the efficacy cisplatin-based chemotherapy in patients with HCC.