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目的探讨新辅助化疗(NACT)对非小细胞肺癌(NSCLC)P-糖蛋白(P-gp)、肺耐药相关蛋白(LRP)、多药耐药相关蛋白(MRP)和谷胱甘肽转移酶S(GST-π)定量表达的影响。方法应用组织芯片、免疫组化及图像定量分析技术,对92例NSCLC标本(其中52例未经化疗的直接手术标本,20例同时具备化疗前活检标本和化疗后手术标本)中P-gp、LRP、MRP和GST-π的表达进行了检测。结果P-gp、LRP、MRP和GST-π在未经化疗的标本中,阳性表达率分别为68.06%,72.22%,81.94%,83.33%;P-gp、LRP和GST-π在腺癌中的表达强度均高于鳞癌(P<0.05,P<0.001,P<0.001),MRP的表达在腺、鳞癌间差异无显著性(P>0.05)。新辅助化疗后,P-gp、GST-π平均光密度与积分光密度在不同临床分期、组织学类型、分化程度、肿瘤大小、年龄以及淋巴结有无转移组中,均高于化疗前(P<0.05或P<0.001);而LRP、MRP平均光密度与积分光密度在上述各组中,在新辅助化疗前、后,差异均无显著性(P>0.05)。结论肺腺癌的原发耐药性可能强于鳞癌;新辅助化疗可能通过诱导耐药蛋白的表达增加肺癌组织的获得性耐药;新辅助化疗的采用与否应视不同病人的具体情况而定,Ⅰ～Ⅱ期NSCLC采用新辅助化疗应慎重,以免影响术后化疗效果;检测NSCLC新辅助化疗前、后耐药蛋白的定量表达,对术前及术后个性化化疗方案的选择和实施具有重要的指导意义。
Objective To investigate the effect of neoadjuvant chemotherapy (NACT) on the expression of P-gp, LRP, MRP and GSK in non-small cell lung cancer (NSCLC) Effect of quantitative expression of enzyme S (GST-π). Methods Tissue microarray, immunohistochemistry and quantitative image analysis were used to detect the expression of P-gp in 92 cases of NSCLC (including 52 cases of direct surgical specimens without chemotherapy, 20 cases of both pre-chemotherapy biopsy specimens and post-chemotherapy surgical specimens) LRP, MRP and GST-π expression were detected. Results The positive rates of P-gp, LRP, MRP and GST-π in non-chemotherapy group were 68.06%, 72.22%, 81.94% and 83.33% respectively. The positive rates of P-gp, LRP and GST- (P <0.001, P <0.001). The expression of MRP was not significantly different between adenocarcinoma and squamous cell carcinoma (P> 0.05). Neoadjuvant chemotherapy, P-gp, GST-π average optical density and integral optical density in different clinical stage, histological type, degree of differentiation, tumor size, age and lymph node metastasis were higher than before chemotherapy (P <0.05 or P <0.001). However, the average optical density and integral optical density of LRP, MRP in each group were not significantly different before and after neoadjuvant chemotherapy (P> 0.05). Conclusions The primary drug resistance of lung adenocarcinoma may be stronger than that of squamous cell carcinoma. Neoadjuvant chemotherapy may increase the acquired drug resistance of lung cancer by inducing the expression of drug resistance protein. The use of neoadjuvant chemotherapy should depend on the specific situation of different patients However, Ⅰ ~ Ⅱ NSCLC neoadjuvant chemotherapy should be cautious, so as not to affect the postoperative chemotherapeutic effect; NSCLC neoadjuvant chemotherapy before and after the quantitative expression of drug resistance, preoperative and postoperative personalized chemotherapy regimens and Implementation has important guiding significance.