非小细胞肺癌多药耐药及其与神经内分泌分化的相关性研究

Multidrug resistance and its relationship with neuroendocrine differentiation in non-small cell lung carcinoma

目的 检测非小细胞肺癌 (NSCLC)多药耐药 (MDR)有关蛋白的表达 ,探讨其与神经内分泌 (NE)分化的关系。方法 采用链霉亲和素 过氧化酶连接 (SP)免疫组化法检测 113例NSCLC中谷胱甘肽S转移酶π(GST π)、多药耐药相关蛋白 (MRP)、肺耐药相关蛋白 (LRP)、神经元特异性烯醇化酶 (NSE)、突触素 (SYN)和嗜铬素A(CgA)的表达。结果 (1)NSCLC中MRP和LRP的表达与组织学类型有关 (P <0 0 5 )。GST π与MRP、MRP与LRP表达之间呈显著相关 (P <0 0 5 )。 (2 )NSCLC中NSE、SYN、CgA的阳性率分别为 5 3 1%、2 6 6%、6 2 %。至少有 2种NE标记物表达者有 2 4例 (2 1 2 % ) ,其表达与肿瘤的分化程度有关 (P <0 0 5 )。 (3 ) 3种MDR有关蛋白在至少有 2种NE标记物阳性组的表达均较阴性组为低 (P <0 0 5 )。结论 GST π、MRP和LRP的过表达是NSCLC产生原发性多药耐药的重要原因。

Objective To study the multidrug resistance(MDR)of non small lung cancer (NSCLC)and its relationship with neuroendocrine(NE)differentiation Methods NSCLC samples from 113 untreated patients were analyzed immunohistochemically with antibodies to glutathion s transferase π(GST π), multidrug resistance associated protein(MRP), lung resistance associated protein(LRP), neuro specific enolase(NSE),synaptophysin(SYN)and chromogranin(CgA) Results (1) The expression of the three proteins was significantly associated with the type of lung carcinoma( P <0 05), but not with the differentiation and lymph node metastasis The expression of GST π was significantly related with MRP, MRP and LRP( P <0 05).(2) The positive rates of the NE markers were : NSE, 53 1%; SYN, 26 6%; CgA, 6 2%; and 21 2% for at least two markers The expression of at least 2 markers was associated with the degree of differentiation( P <0 05), but not with the type of lung cancer and lymph node metastasis (3)The expression of the three multidrug resistance related proteins in the positive group for at least 2 markers was significantly lower than that in the negative group( P <0 05).Conclusions The over expressions of GST π, MRP and LRP are important causes of primary multidrug resistance in NSCLC The differentiation of NE may be one of the factors involved in multidrug resistance