Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Oncol Rep. 2010 Apr;23(4):965-72. doi: 10.3892/or_00000721.
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 necrosis 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. Overexpression of MRP2 was detected in 24/46 (52%) tumor specimens. In 16 patients treated with cisplatin, tumor size 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 correlates with a 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. Expression of MRP2 determines the efficacy of cisplatin-based chemotherapy in patients with HCC.
我们假设多药耐药相关蛋白 2（MRP2）的表达，作为顺铂的主要转运蛋白，可能决定顺铂治疗肝细胞癌（HCC）患者的疗效。对 49 例连续接受 HCC 切除术的患者进行了前瞻性分析（16 例接受顺铂为基础的新辅助化疗，33 例未接受新辅助化疗）。通过免疫组织化学和 Western blot 分析评估切除标本中 MRP2 的表达。每位患者肿瘤标本的最大直径通过组织学评估肿瘤坏死程度。肿瘤坏死的中位数百分比为 81%（范围：0-100%），3 例患者完全坏死。46 例肿瘤标本中有 24 例（52%）检测到 MRP2 过表达。在接受顺铂治疗的 16 例患者中，肿瘤大小和顺铂剂量与切除标本的肿瘤坏死无相关性（分别为 P=0.706 和 P=0.555）。在接受顺铂治疗的 16 例患者的 13 例含有肿瘤的肿瘤标本中，有 8 例存在 MRP2 过表达。MRP2 过表达的肿瘤标本的肿瘤坏死百分比低于非过表达的肿瘤标本（中位数肿瘤坏死百分比，19% vs. 99%，P=0.003）。总之，MRP2 过表达与接受顺铂为基础的新辅助化疗的 HCC 患者的肿瘤坏死百分比降低相关，而肿瘤大小或顺铂剂量与肿瘤坏死百分比无关。MRP2 的表达决定了 HCC 患者顺铂为基础化疗的疗效。
