Effects of neoadjuvant chemotherapy on the quantitative expression of P-gp, LRP, MRP, GST-π in NSCLC and its clinical significance.

BACKGROUND: Neoadjuvant chemotherapy (NACT) plays an important role in systemic chemotherapy for non-small cell lung cancer (NSCLC). P-glycoprotein (P-gp), lung resistance related protein (LRP), multidrug resistance-associated protein (MRP) and glutathione S-transferase (GST-π) may be associated to drug resisitance to chemotherapy in NSCLC. The aim of this study is to investigate the expressions of P-gp, LRP, MRP and GST-π in samples from NSCLC patients before and after treatment with NACT, and their quantitative changes, so that to evaluate the influence of NACT on drug resistance to chemotherapy of NSCLC.

METHODS: Total 92 specimens from 72 cases of NSCLC, including 52 samples of surgery excision from non-NACT-treated patients and 20 paired samples before and after NACT from the same patient, were studied. The expression of P-gp, LRP, MRP and GST-π was detected with tissue chip technique and immunohistochemistry. The quantitative analysis was carried out by computer image analysis system..

RESULTS: In the samples before NACT, the positive rate of P-gp, LRP, MRP, GST-π expression was 66.67% (48/72), 72.22% (52/72), 81.94% (59/72), 83.33% (60/72), respectively. The expressive intensity of P-gp, LRP and GST-π was significantly stronger in adenocarcinoma than that in squamous cell carcinoma (P < 0.05, P < 0.001, P < 0.001, respectively); there was no significant difference in the expression of MRP between adenocarcinoma and squamous cell carcinoma (P > 0.05). In samples after treatment with NACT, the expression of P-gp, GST-π demonstrated by average optical density (AOD) and integral optical density (IOD) were significantly higher (P < 0.05, P < 0.001 respectively) than that in biopsied samples taken before NACT; The change in expression of P-gp, GST-π was also showed difference by different histopathological types, differentiations, 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) in the expression of LRP and MRP demonstrated by both of AOD and IOD.

CONCLUSIONS: The results suggest that drug resistance in adenocarcinoma is primarily stronger than that in squamous cell carcinoma. NACT may enhance acquired drug resistance of NSCLC through inducing the expression of drug resistance protein. The results indicate that acquired drug resistance must be considered with the application of NACT to NSCLC patient in clinic, especially to patient in stage I and II. Since NACT may lead to the enhancement of acquired drug resistance in stage I and II, this may dwindle the therapeutic effect of chemotherapy after surgery. Comparative examination of drug resistance proteins before and after NACT, combining with comprehensive consideration of chemical regimens of NACT, should be recommended during chemotherapy of NSCLC for both before and after surgery.