Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma

作者：Korita Pavel V; Wakai Toshifumi^*; Shirai Yoshio; Matsuda Yasunobu; Sakata Jun; Takamura Masaaki; Yano Masahiko; Sanpei Ayumi; Aoyagi Yutaka; Hatakeyama Katsuyoshi; Ajioka Yoichi

来源：Oncology Reports, 2010, 23(4): 965-972.

DOI：10.3892/or_00000721

• hepatocellular carcinoma
• drug resistance
• multidrug resistance-associated protein 2
• chemotherapy
• cisplatin

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.

• 出版日期2010-4