Expression And Clinical Significance Of P53 And COX-2 Protein In Patients With EGFR Mutant Advanced Lung Adenocarcinoma

Background and Objectives:In recent years,the applications of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs),such as gefitinib or erlotinib,for patients with EGFR mutant advanced lung adenocarcinoma have become models for the molecular targeted therapy for lung cancer.Several clinical studies have shown that the first-line EGFR-TKIs treatment has a significant advantage in objective response rate(ORR)and progression-free survival(PFS),which is compared with the platinum-based chemotherapy in patients with EGFR mutant advanced lung adenocarcinoma.However,inevitably,the majority of patients treated with EGFR-TKIs will suffer from drug resistance after 8 to 16 months,then have a disease progression,which is one of the challenges for clinical treatment.Thus,finding appropriate biomarkers to predict the effects of EGFR-TKIs and guide subsequent treatment is particularly important.Even though P53 protein or COX-2 protein can have a directly or indirectly influence on the disease progression,researches on the predictive effects of EGFR-TKIs are still insufficient.This research is made through the method of the immunohistochemical staining to investigate the expression of p53 and COX-2protein in patients with EGFR mutant advanced lung adenocarcinoma and their correlation with clinical characteristics,and evaluate their predictive significance for the effects of EGFR-TKIs.Materials and Methods We collected the paraffin specimens of EGFR mutant advanced lung adenocarcinoma issue from 43 patients in the Second Affiliated Hospital of Zhengzhou University from March 1,2014 to January 31,2016.The immunohistochemistry staining was used to examine the expression of p53 and COX-2 proteins in tissues of 43 patients with EGFR mutant advanced lung adenocarcinoma.Chi-square test was utilized to analyze the relationship between p53 or COX-2 expression and clinical characteristics.Prognosis was examined by Kaplan-Meier and Log-rank test.The Cox proportional hazards model was used to estimate the factors that may affect the PFS.Results1.The positive expression rates of p53 and COX-2 in 43 patients with EGFR mutant advanced lung adenocarcinoma were 41.8%,53.4%,respectively.The positive expression of p53 protein is associated with age(?2 = 3.939,P = 0.047)and differentiation degree(?2 = 4.182,P = 0.041).While,the positive expression of COX-2 protein had no significant differences in age,sex,smoking history,differentiation degree,clinical stage or EGFR mutation types(P >0.05).2.The expression of p53 and COX-2 protein had no significant correlation with each other(P >0.05).3.The median PFS in p53-negative and p53-positive patients with EGFR mutant advanced lung adenocarcinoma treated with EGFR-TKIs were 12.0 months,7.5 months,which has a statistically significant difference(?2 = 4.726,P = 0.030).The median PFS in COX-2-negative and COX-2-positive patients with EGFR mutant advanced lung adenocarcinoma treated with EGFR-TKIs were 12.0 months,10.0months,which also has a statistically significant difference(?2 = 5.578,P = 0.018).4.Multivariate analysis revealed that the expression of p53(HR = 0.450,P= 0.046)and COX-2(HR = 0.424,P = 0.021)were independent prognostic factors for EGFR mutant advanced lung adenocarcinoma patients treated with EGFR-TKIs.CONCLUSION1.The older or less poorly differentiation degree the patients are,the more the positive expression of p53 protein will be likely increasing.After the treatment of EGFR-TKI in patients with EGFR mutant advanced lung adenocarcinoma,the median PFS in the p53-negative patients is longer than the p53-positive patients.2.After the treatment of EGFR-TKI in patients with EGFR mutant advanced lung adenocarcinoma,the median PFS in the COX-2-negative patients is longer than the COX-2-positive patients.3.The expression of p53 or COX-2 may be negative predictive factor in EGFR mutant advanced lung adenocarcinoma patients treated with EGFR-TKI.