表皮生长因子受体和多药耐药蛋白在非小细胞肺癌中的表达及其与化学药物治疗疗效的相关性

Expressions of EGFR and MRPs in NSCLC and their correlations with effect of chemotherapy

摘要:

目的  探讨表皮生长因子受体（EGFR）与多药耐药蛋白（MDR）在非小细胞肺癌中的表达及与化学药物治疗（以下简称化疗）疗效的相关性。方法  采用免疫组织化学二步法检测95例非小细胞肺癌（NSCLC）组织和15例正常肺组织中EGFR与肺耐药蛋白（LRP）、P-糖蛋白（P-gp）、多药耐药相关蛋白（MRP）及谷光甘肽转移酶（GST-π）的表达。结果  95例NSCLC中，EGFR、LRP、P-gp、MRP及GST-π在NSCLC组织中的阳性表达率分别为50.53%、60.00%、40.00%、41.05%和55.79%。EGFR表达在有无吸烟史、不同病理类型（鳞癌vs腺癌）、不同TNM分期及有无淋巴结转移的NSCLC患者间比较，差异有统计学意义（P <0.05）。LRP和MRP在腺癌中的阳性表达率高于鳞癌（P <0.05），MRP在高分化癌的表达阳性率低于中、低分化（P <0.05）。MRP与LRP、P-gp与GST-π的表达呈正相关（r =0.341，P =0.001；r =0.213，P =0.038），EGFR与LRP、P-gp、MRP、GST-π的表达无关（P >0.05）。EGFR阳性表达的化疗有效率为37.5%，低于EGFR阴性表达的化疗有效率（66.0%）（P <0.05）。结论  NSCLC组织中EGFR与多药耐药蛋白常阳性表达，形成MDR的4种蛋白相互联系，可能对耐药的形成起协同作用，EGFR可以作为评价NSCLC化疗疗效的客观指标。

Abstract:

Objective To investigate the expressions of epidermal growth factor receptor (EGFR) and multi-drug resistance-associated protein (MRP), and their relationships with efficacy of chemotherapy in non-small cell lung cancer (NSCLC). Methods Immunohistochemistry (EnVision method) was used to detect the expressions of EGFR, lung resistance protein (LRP), P-glycoprotein (P-gp), MRP and glutathione S-transferase π (GST-π) in NSCLC tissues of 95 patients and 15 normal lung samples. Results The positive-expression rates of EGFR, LRP, P-gp, MRP and GST-π in the NSCLC were 50.53%, 60.00%, 40.00%, 41.05% and 55.79% respectively. EGFR in the NSCLC tissues was significantly correlated with the history of smoking, pathological types of cancer (squamous cell carcinoma vs adenocarcinoma), presence of lymph node metastasis and TNM stages (P < 0.05). The positive-expression rates of LRP and MRP in the adenocarcinomas were higher than those in the squamous cell carcinomas (P < 0.05), and the expression rate of MRP in the well-differentiated carcinomas was higher than that in the medium- and poorly-differentiated carcinomas (P < 0.05). There were positive correlations between the expressions of MRP and LRP, P-gp and GST-π in the NSCLC (r = 0.341, P =0.001; r = 0.213, P = 0.038). EGFR had no correlation with LRP, P-gp, MRP or GST-π (P > 0.05). The chemotherapy efficiency for the EGFR-negative NSCLC was 66.0%, which was significantly higher than that for the EGFR-positive NSCLC (37.5%, P < 0.05). Conclusions EGFR and MRP are over-expressed in NSCLC tissues. Multidrug resistance proteins have synergistic effects on drug resistance. EGFR could be used to objectively predict chemotherapy effect and prognosis of NSCLC.