Department of Thoracic Surgery, Cancer Hospital of Sichuan Province, No. 55, 4th section of Remin South Rd, Chengdu, 610000, Sichuan province, China,
Pathol Oncol Res. 2013 Oct;19(4):641-8. doi: 10.1007/s12253-013-9623-3. Epub 2013 Mar 19.
Studies have demonstrated that radical esophagectomy can significantly prolong disease-free survival and improve the survival rate of patients with T3 or T4 esophageal cancer and lymph node metastasis. Multidrug resistant cancer cells have active efflux mechanisms that prevent the accumulation of chemotherapeutic drugs in the cells. The purpose of this study was to compare the expression of five MDR related proteins between primary tumors in patients with thoracic esophageal squamous cell carcinoma (ESCC) and metastatic cancer in lymph nodes to explore the clinical significance of heterogeneity in MDR metastatic cancer cells. Fifty-four patients with ESCC and lymph node metastasis were included. All patients underwent subtotal esophagectomy and D2/D3 lymph node resection. The expression of lung resistance-related protein (LRP), P-glycoprotein, topoisomerase-II, thymidylate synthase, and glutathione S-transferase P1-1 (GST-π) were determined in the primary tumors and lymph nodes via immunohistochemistry. The expression of LRP was significantly different between the primary tumors and lymph nodes (P = 0.026). No significant differences were found for the other four proteins, and protein expression was not associated with either degree of differentiation or disease stage. It was also found that GST-π was expressed in all patients in both the primary tumors and lymph nodes, suggesting that the design and application of chemotherapeutic protocols capable of reducing GST-π expression may be beneficial for patients with ESCC. Additional research regarding the clinical utility of MDR protein expression in ESCC is warranted to design effective chemotherapeutic protocols.
研究表明,根治性食管切除术可显著延长 T3 或 T4 期食管鳞癌伴淋巴结转移患者的无病生存期和生存率。多药耐药癌细胞具有活跃的外排机制,可防止化疗药物在细胞内积聚。本研究旨在比较胸段食管鳞癌(ESCC)原发肿瘤和淋巴结转移癌中五种多药耐药相关蛋白的表达,以探讨多药耐药转移性癌细胞异质性的临床意义。纳入 54 例 ESCC 伴淋巴结转移患者。所有患者均行食管次全切除术和 D2/D3 淋巴结清扫术。采用免疫组织化学法检测原发肿瘤和淋巴结中肺耐药相关蛋白(LRP)、P-糖蛋白、拓扑异构酶-II、胸苷酸合成酶和谷胱甘肽 S-转移酶 P1-1(GST-π)的表达。LRP 在原发肿瘤和淋巴结中的表达差异有统计学意义(P=0.026)。其他四种蛋白的表达差异无统计学意义,且蛋白表达与分化程度或疾病分期均无关。此外,还发现 GST-π 在原发肿瘤和淋巴结中均在所有患者中表达,提示设计和应用能够降低 GST-π 表达的化疗方案可能对 ESCC 患者有益。需要进一步研究 ESCC 中多药耐药蛋白表达的临床应用价值,以设计有效的化疗方案。