Quantitative Expression Of Of P-glycoprotein, Lung Resistance Related Protein, Multidrug Resistance-associated Protein And Glutathione S-transferase Expressions In Non-small Cell Lung Cancer And Its Clinical Significance

Objective To investigate the expressions of P-glycoprotein (P-gp), lung resistance related protein (LRP), multidrug resistance-associated protein (MRP) and Glutathione S-transferase (GST-π) in samples from NSCLC patients before and after treated with neoadjuvant chemotherapy (NACT), and their quantitative changes, so that to evaluate the influence of NACT on drug resistance to chemotherapy of NSCLC. Methods 92 cases of NSCLC, including 52 excisional cases pre-chemotherapy and 20 paired samples before and after neoadjuvant chemotherapy were examined with tissue chip techniques and immunohistochemistry. The quantitations of P-gp, LRP, MRP and GST-πexpressions were assessed by computer image analysis system. Results The positive rates of P-gp, LRP, MRP, GST-πexpression were 65.22%, 76.09%, 81.52%, 84.78% respectively in untreated NSCLC. In untreated samples, P-gp, MRP and GST-πexpressions were higher in adenocarcinoma than in squamous cell carcinoma (P＜0.05, P＜0.001, P＜0.001 respectively). Their expressions were all higher in well differentiated group than in poorly differentiated group, and the expressions decreased with the differentiation grade decreasing (P＜0.05). The expression of MRP was not associated with the tissue type and differentiation grade(P＞0.05). All of them were not related to the age, size, clinical stage and lymph node metastasis (P＞0.05). In samples after treated with NACT, the expression of P-gp, GST-πdemonstrated by average optical density and integral optical density were significantly higher (P＜0.05, P＜0.001 respectively) compared with that of biopsy samples taken before NACT; The change in expression of P-gp, GST-πwas also showed difference in histopathological types, differentiation, ages, sizes, clinical stages as well as lymph node metastasis or not(P＜0.05 or P＜0.001). There was no significant difference between samples taken before and after NACT (P＞0.05) with the expression of LRP and MRP demonstrated by both of average optical density and integral optical density. Conclusions (1) This study implies that expressions of P-gp, LRP and GST-πare related to tissue type and differentiation grade before chemotherapy. Their expressions in adenocarcinoma are primarily stronger than those in squamous cell carcinoma. Meanwhile, their expressions were all higher in well differentiated group than in poorly differentiated group. (2) Expressions of P-gp and GST-πincrease noticeably after NACT. NACT may enhance acquired drug resistance of NSCLC through inducing the expression of drug resistance protein. (3) Since NACT may lead to the enhancement of acquired drug resistance inⅠ-Ⅱstage of NSCLC, this may dwindle the therapeutic effect of chemotherapy after surgery. So that acquired drug resistance must be considered with the application of NACT to NSCLC patient in clinic, especially to patient inⅠ-Ⅱstage of NSCLC. (4) Comparative examination of drug resistance proteins before and after NACT, combining with comprehensive consideration of chemical regimens of NACT is recommended during chemotherapy of NSCLC for both before and after surgery.