多药耐药相关蛋白在食管鳞癌原发灶与淋巴结转移灶中的差异表达及意义

doi:10.3969/j.issn.1007-3969.2014.1.003

中国癌症杂志 ›› 2014, Vol. 24 ›› Issue (1): 15-20.doi: 10.3969/j.issn.1007-3969.2014.1.003

多药耐药相关蛋白在食管鳞癌原发灶与淋巴结转移灶中的差异表达及意义

方强¹,董丹丹²,杨红²,任光国¹,韩泳涛¹,肖波¹

1.四川省肿瘤医院胸外科，四川成都610041；
2.四川省人民医院病理科，四川成都610072

出版日期:2014-01-30 发布日期:2014-02-14
通信作者: 方强　E-mail:flank716@163.com
基金资助:
四川省卫生厅科研基金(No：090541)

The heterogenous expression and significance of multidrug resistance-associated proteins in primary tumors and metastatic lymph nodes in patients with esophageal squamous cell carcinoma

FANG Qiang¹,DONG Dan-dan²,YANG Hong²,REN Guang-guo¹,HAN Yong-tao¹,XIAO Bo¹

1.Department of Thoracic Surgery, Sichuan Cancer Hospital, Chengdu Sichuan 610041, China;
2.Department of Pathology, the People’s Hospital of Sichuan, Chengdu Sichuan 610072, China

Published:2014-01-30 Online:2014-02-14
Contact: FANG Qiang E-mail: flank716@163.com

摘要/Abstract

摘要： 背景与目的：食管癌术后辅助化疗主要针对淋巴结转移灶，但转移灶中肿瘤细胞群多药耐药(multidrug resistance，MDR)的异质性是影响化疗效果的一个主要因素。目前有关食管鳞癌MDR的研究多限于肿瘤原发灶，其原发灶与淋巴结转移灶MDR是否存在异质性鲜见报道。本研究探讨MDR相关蛋白在食管鳞癌原发灶与淋巴结转移灶中的差异表达及意义。方法：对54例食管胸段鳞癌原发灶及相应淋巴结转移灶分别进行MDR相关蛋白肺耐药相关蛋白(LRP)、P-糖蛋白(P-gp)、拓扑异构酶Ⅱ(TOPO-Ⅱ)、胸甘酸合成酶(TS)、谷胱甘肽-S-转移酶(GST-π)免疫组织化学染色，比较同一患者MDR相关蛋白在肿瘤原发灶和淋巴结转移灶中表达和耐药的差异，分析其与组织分化程度的关系。结果：肿瘤原发灶与淋巴结转移灶LRP、P-gp、TS、TOPO-Ⅱ、GST-π表达和耐药不一致率分别为63.0%和26.9%、42.6%和22.2%、48.1%和25.9%、50.0%和29.6%、18.5%和1.9%。LRP在原发灶与淋巴结转移灶的表达差异有统计学意义(P=0.026)，其余4种蛋白在原发灶与淋巴结转移灶的表达没有差异，GST-π在原发灶与淋巴结转移灶中均表达。MDR相关蛋白表达与组织分化程度无关。结论：食管鳞癌原发灶与淋巴结转移灶存在MDR的异质性现象。对淋巴结转移灶检测MDR相关蛋白表达水平有助于指导食管鳞癌术后选择合理的化疗方案。

关键词: 食管肿瘤, 淋巴结转移, 多药耐药性

Abstract: Background and purpose: Postoperative chemotherapy targets the metastatic cancer in the remaining lymph nodes, but the heterogeneity in multidrug resistance (MDR) of metastatic cancer cells is a main factor affecting chemotherapeutic efficacy. Recent studies only examined the primary lesion of esophageal squamous cell carcinoma(ESCC). There is no report about heterogeneity between the primary tumor and metastases lymph node. The purpose of this study was to explore the heterogenous expression and clinical significance of multidrug resistance (MDR) associated proteins in primary tumors and metastatic lymph nodes in patients with thoracic ESCC. Methods: The expressions of lung cancer associated resistance protein (LRP), P-glycoprotein (P-gp), topoisomeraseⅡ (TOPO-Ⅱ), thymidylate synthase (TS), glutathione S-transferase-π (GST-π) were examined by immunohistochemistry in primary lesions and corresponding metastatic lymph nodes in 54 patients with thoracic ESCC. The differences between expression of primary lesions and matched metastatic lymph nodes were compared and analyzed in relationship with tissue differentiation degree. Results: The discordant rates of the expression and drug resistance between primary lesions and corresponding metastatic lymph nodes in LRP, P-gp, TS, TOPO-Ⅱ and GST-π were 63.0% and 26.9%, 42.6% and 22.2%, 48.1% and 25.9%, 50.0% and 29.6%, 18.5% and 1.9% respectively. The expression of LRP showed significant difference between the primary tumors and lymph nodes (P=0.026). No significant differences were found for the other four proteins, and GST-π was expressed in all patients in both the primary tumors and lymph nodes. Protein expression was not associated with degree of differentiation. Conclusion: There is evident of heterogenous expression of MDR associated proteins in metastatic lymph nodes compared to the primary tumors of ESCC. The examination of expression levels of MDR associated proteins in metastatic lymph nodes is helpful to select the postoperative rational chemotherapy plan.

Key words: Esophageal neoplasms, Lymph nodes metastasis, Multidrug resistance

方强,董丹丹,杨红,任光国,韩泳涛,肖波. 多药耐药相关蛋白在食管鳞癌原发灶与淋巴结转移灶中的差异表达及意义[J]. 中国癌症杂志, 2014, 24(1): 15-20.

FANG Qiang,DONG Dan-dan,YANG Hong,REN Guang-guo,HAN Yong-tao,XIAO Bo. The heterogenous expression and significance of multidrug resistance-associated proteins in primary tumors and metastatic lymph nodes in patients with esophageal squamous cell carcinoma[J]. China Oncology, 2014, 24(1): 15-20.

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多药耐药相关蛋白在食管鳞癌原发灶与淋巴结转移灶中的差异表达及意义

The heterogenous expression and significance of multidrug resistance-associated proteins in primary tumors and metastatic lymph nodes in patients with esophageal squamous cell carcinoma

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