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

Abstract

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.

• Authors: Pavel V Korita, Toshifumi Wakai, Yoshio Shirai, Yasunobu Matsuda, Jun Sakata, Masaaki Takamura, Masahiko Yano, Ayumi Sanpei, Yutaka Aoyagi, Katsuyoshi Hatakeyama, Yoichi Ajioka
• Journal: Oncology reports (Oncol Rep) Vol. 23 Issue 4 Pg. 965-72 (Apr 2010) ISSN: 1791-2431 [Electronic] Greece
• PMID: 20204280 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• ABCC2 protein, human
• Antineoplastic Agents
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins
• Cisplatin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage)
• Blotting, Western
• Carcinoma, Hepatocellular (drug therapy, genetics, pathology)
• Cisplatin (administration & dosage)
• Drug Resistance, Neoplasm (genetics)
• Female
• Humans
• Immunohistochemistry
• Liver Neoplasms (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins (biosynthesis, genetics)
• Necrosis
• Neoadjuvant Therapy
• Neoplasm Staging
• Pilot Projects