Molecular Predictive Markers In The Treatment Of Gefitinib In Patients With Lung Adennocarcinoma

Objective:Lung cancer is the leading cause of cancer deaths in China and worldwide.Non-small-cell lung cancer (NSCLC) accounts for about 80% in which 70%-80% are advanced cases.Epidermal growth factor receptor (EGFR) is one of the focus targets for molecular targeted therapy. Gefitinib is a kind of effective EGFR tyrosine-kinase inhibitor (TKI).This experiment is to find the molecular predictive markers in the treatment of gefitinib in patients with advanced lung adenocarcinoma, such as EGFR mutation and the expression of VEGF.Methods:30 paraffin embedded blocks from 30 patients who were diagnosed as advanced lung adenocarcinoma by histological examination. At first, the tissue DNA was abstracted, and then the exons 19 and 21 in EGFR gene were subjected for PCR amplification and direct sequencing. The expressions of VEGF were detected by immunohistochemistry. Evaluate the response rate (RR) using RECIST criteria and record the duration of progression-free survival (PFS).Results:1.EGFR mutations are found in 10 cases (33.3%). Mutations of exon 19 are 4 cases while exon 216 cases.There is statistically significant difference between the mutations and non mutations in gender (P=0.049),and there was no difference in age(P=0.431) and staging (P=1.000).2.The mutation rate is 80% in the effective cases and 10% in the invalid cases,the difference is significant (P< 0.05).The median PFS is 10.5 months in the cases of mutation and 3.0 months in non mutation, the difference is significant (x2=8.666,P=0.003).3.In 30 patients,VEGF expressing (-) is 9 cases,(+) is 6 cases,(++) is 6 cases,(+++) is 5 cases,(++++) is 4 cases. There is no significant correlation between the level of VEGF expression and the clinical factors of gender(Z=0.397,P=0.703),age(Z=0.023,P=1.000)and clinical staging (Z=0.687,P=0.509)4.The overall response rate and disease controlled rate of gefitinib is 33.3% and 60.0% respectively.The level of VEGF expression is significantly different between the effective cases and invalid cases (P=0.013). In the effective cases, the level of VEGF expression is lower than in the invalid cases.5.There is no significant correlation between EGFR mutations and VEGF expressions (Z=0.925,P=0.373).Conclusion:1. The response rate of gefitinib in the EGFR mutation patients is higher than in the patients who have no EGFR mutation. EGFR mutation is a good molecular predictor in the treatment of gefitinib in patients with advanced lung adenocarcinoma.2. The level of VEGF expression can predict the prognosis of patients patients with advanced lung adenocarcinoma.