Application Value Of EGFR Mutant Protein Expression In Targeted Therapy With Tyrosine Kinase Inhibitors In Advanced Lung Adenocarcinoma

Objective : This study retrospectively analyzed the efficacy of first-generation EGFR-TKI in stage IV lung adenocarcinoma patients with positive EGFR gene mutation combined with corresponding EGFR mutant protein expression,and also investigated the incidence of T790 m mutation after first-generation EGFR-TKI resistance.Methods : Paraffin-embedded tissue samples were retrospectively collected from patients with stage IV lung adenocarcinoma known to have EGFR gene mutation who visited the First Affiliated Hospital of Anhui Medical University and the Second Affiliated Hospital of Anhui Medical University from January 1,2018 to March 30,2021.The expression of EGFR protein was detected by immunohistochemical（IHC） using rabbit monoclonal antibodies against corresponding mutated proteins.We analyzed the relationship between the expression of EGFR protein and the efficacy of the first-generation EGFR-TKI.This study analyzed the efficacy of the first-generation EGFR-TKI in stage IV lung adenocarcinoma patients with positive EGFR gene mutation combined with corresponding EGFR mutant protein expression.The incidence of T790 M mutation after the first-generation EGFR-TKI resistance was investigated.Results:1.Among 69 patients with stage IV lung adenocarcinoma who met the admission criteria,29 patients had EGFR 19 exon deletion mutation,of which the positive rate of EGFR 19 exon deletion mutation protein expression was 37.93%.The median PFS was 13.20 months in the positive group and 13.00 months in the negative group（X~2 = 0.405,P=0.817）.There were 40 patients with EGFR 21 exon L858 R point mutation,and the positive rate of L858 R point mutation protein expression was 70.00%.The median PFS was 12.13 months in the positive group and 11.93 months in the negative group（X~2 =0.191,P=0.909）,respectively.There were no significant differences between protein expression and efficacy.2.The mutation rates of T790 M in patients with EGFR 19 exon deletion and L858 R point mutation were 37.93% and 42.50% respectively after the first-generation EGFR-TKI resistance.Among patients with exon 19 deletion,the T790 M mutation rate was 63.64% and 22.22% in the positive and negative groups（X~2 = 4.974,P=0.026）,respectively.In patients with L858 R point mutation,the T790 M mutation rate after drug resistance was 53.57% in the positive group and 16.67% in the negative group（X~2 =4.682,P=0.030）.The differences were statistically significant.Conclusion1.In patients with EGFR-mutation-positive advanced lung adenocarcinoma,EGFR mutant protein expression had no predictive value for the first-generation EGFR-TKI efficacy.2.The first-generation EGFR-TKI resistance mediated by T790 M mutation is more common in patients with positive expression of corresponding mutant protein.