作者：王霞 王培源 吴淑华 于宁 牟清海
【摘要】 目的 探讨肺耐药蛋白（lung resistance protein, LRP），DNA拓扑异构酶Ⅱ（topoisomeraseⅡ, TOPOⅡ），谷胱甘肽?S?转移酶?π（glutathione?S?transferase?π, GST?π）在非小细胞肺癌（non?small cell lung cancer, NSCLC）的表达及其临床意义。方法采用免疫组化技术（S?P法）检测57例术前均未进行化疗的非小细胞肺癌中LRP、TOPOⅡ及GST?π的表达情况。结果 在NSCLC中LRP、TOPOⅡ及GST?π的表达阳性率分别为68.42%（39/57），66.67%（38/57）和84.21%（48/57），三者的表达均与病人的年龄、性别、肿瘤的大体类型、淋巴结转移以及临床分期无关（P＞0.05），而与肿瘤的分化程度相关，高中分化与低分化之间差异有显著性（P＜0.05）。且TOPOⅡ表达与组织学类型相关，鳞癌组的表达显著高于腺癌和细支气管肺泡癌（P＜0.05）。结论 LRP、GST?π和TOPOⅡ共同参与了NSCLC的固有耐药，表达的差异提示对药物敏感度不同，联合检测为制定科学有效的治疗方案具有临床意义。
【关键词】 肺耐药蛋白；DNA拓扑异构酶Ⅱ；谷胱甘肽?S?转移酶?π；非小细胞肺癌；多药耐药性
【Abstract】 Objective To investigate the expression and evaluate clinical significances of lung resistance protein (LRP), topoisomeraseⅡ(TOPOⅡ), glutathione?S?transferase?π (GST?π) in non?small cell lung cancer (NSCLC).Methods Immunohistochemical S?P method was used to examine the expression of LRP, TOPOⅡ and GST?π in 57 NSCLC cases.Results The positive rates of LRP, TOPOⅡ and GST?π in NSCLC were 68.42%(39/57)，66.67%(38/57) and 84.21%(48/57),which were not correlated with age, sex, position, lymph node metastasis and TNM stage（P＞0.05）. The positive rates were correlated with the degree of tumor differentiation, the poorly differentiated carcinomas were significantly different with well-differentiated and moderately differentiated carcinomas（P＜0.05）. And the expression of TOPOⅡ was correlated with histological types，the positive rate in squamous?cell carcinoma was higher than that in adenocarcinoma and bronchioalveolar carcinoma（P＜0.05）.Conclusion LRP, TOPOⅡ and GST?π intervene in the original multi?drug resistance together. The expression difference indicates the sensitive difference to pharmaceuticals of NSCLC.The expression status detection of LRP, TOPOⅡ and GST?π is significant for making scientific and efficient clinical treatment plan.
【Key words】 LRP, TOPOⅡ, GST?π, NSCLC, multi?drug resistance
肺癌是最常见的恶性肿瘤之一，近年来发病率和死亡率明显增高，根据其组织学形态可分为小细胞性肺癌（SCLC）和非小细胞肺癌（NSCLC）。NSCLC占所有肺癌的80%～85%，虽然以手术为主的综合性治疗措施不断提高，NSCLC患者的5年生存率仅为15%，这与两种因素有关［1］，一是诊断时间，大约70%NSCLC患者诊断时已经转移或局部侵袭而失去手术机会；二是 NSCLC包含多种分子耐药机制，最常见的是肿瘤组织的多药耐药性（multi?drug resistance, MDR）。MDR基因在肿瘤组织中的异常表达往往导致肿瘤患者化疗的失败，并影响的病情的进展。本文回顾性分析了57例非小细胞肺癌中肺耐药蛋白（LRP）、DNA拓扑异构酶Ⅱ（TOPOⅡ）、谷胱甘肽?S?转移酶?π（GST?π）的表达，探讨其临床意义，为临床治疗方案的制定提供理论指导。