耐药相关基因表达对Ⅲ期非小细胞肺癌新辅助化疗的临床预测价值探讨

Predictive Value of Drug Resistance related Genes Expression in Neoadjuvant Chemotherapy in Patients with Non small Cell Lung Cancer of Stage Ⅲ

背景与目的P-糖蛋白(P-glycoprotein,P-gp)、多药耐药相关蛋白(multidrugresistance-associatedprotein,MRP)、肺耐药蛋白(lungresistanceprotein,LRP)在多药耐药中发挥重要的作用,联合检测它们在评价非小细胞肺癌新辅助化疗中的价值国内外尚未见报道。本研究旨在探讨联合检测P-gp、MRP、LRP对Ⅲ期非小细胞肺癌新辅助化疗敏感性的预测价值。方法应用免疫组化技术检测31例行新辅助化疗的患者化疗前标本及化疗后手术标本。结果化疗前P-gp、MRP、LRP表达的阳性率分别为29.0%(9/31)、45.2%(14/31)及38.7%(12/31),化疗后分别为61.3%(19/31)、51.6%(16/31)及41.9%(13/31)。化疗前MRP和LRP同时阳性者32.3%(10/31),MRP与LRP具相关性(r=0.61,P<0.001)。化疗前P-gp、MRP、LRP表达阳性者化疗有效率分别为44.4%(4/9)、28.6%(4/14)及16.7%(2/12),MRP与LRP同时阳性者有效率为10.0%(1/10)。化疗有效的患者中位生存期为31个月,无效的为15个月,同期直接手术的患者为18个月。结论肿瘤中MRP与LRP共表达者化疗耐药的可能性很大,化疗有效率较低,新辅助化疗意义不大。

BACKGROUND &OBJECTIVE: P glycoprotein (P gp), multidrug resistance associated protein (MRP), and lung resistant protein (LRP) play important roles in multidrug resistance (MDR). This study was to determine P gp, MRP, and LRP expression in patients with non small cell lung cancer (NSCLC) of stageⅢ, and evaluate their predictive value in neoadjuvant chemotherapy. METHODS: Immunohistochemical analyses were performed on 31 patients with NSCLC of stageⅢbefore, and after neoadjuvant chemotherapy. RESULTS: The frequency of P gp, MRP, and LRP expression were 29.0%(9/31), 45.2%(14/31),and 38.7%(12/31) before chemotherapy,and were 61.3%(19/31), 51.6%(16/31), and 41.9%(13/31) after chemotherapy. Of 31 patients, 10 (10/31, 32.3%) expressed both MRP and LRP before chemotherapy, which indicated significant positive correlation between MRP and LRP expression (r=0.061, P< 0.001). In patients with P gp, MRP, or LRP expression before chemotherapy, the response rates towards chemotherapy were 44.4%(4/9), 28.6%(4/14), and 16.7%(2/12). Of 10 patients with both MRP and LRP expression, only 1 (1/10, 10.0%) responded to chemotherapy. The median survival time of patients who responded to chemotherapy was 31 months, while that of patients who did not responded to chemotherapy was 15 months, that of patients who didnt receive neoadjuvant chemotherapy before surgery was 18 months. CONCLUSION: Patients with both MRP and LRP expression are probably resistant to chemotherapy, the value of neoadjuvant chemotherapy is limit in such patients.