The Relationship Between Rare EGFR Mutation And Clinicopathological Features Of Non-small Cell Lung Cancer

Background: The incidence of lung cancer is rising year by year.It has become the leading killer of human health.Non small cell lung cancer(NSCLC)in lung cancer accounts for about 85%.In recent years,molecular targeted therapy has become the first-line treatment for advanced NSCLC patients.Detection of EGFR gene mutation has become an important indicator in the diagnosis and treatment of NSCLC,because the mutation status of EGFR gene has guiding significance for target drug use and prognosis of NSCLC patients.EGFR mutations including common mutations and rare mutations,common mutations in the exon 19 deletion mutation(19del)and L858 R point mutation of exon 21 mutation in EGFR,the total number of about 90%,because the EGFR common mutations to EGFR tyrosine kinase inhibitors(EGFR-TKIs)are very sensitive,so it is also called sensitive mutation.EGFR-TKIs targeted therapy is widely used in the treatment of patients with common EGFR mutations.However,there are few reports about rare mutations in EGFR because of the low incidence of EGFR rare mutations.The clinical efficacy of EGFR-TKIs in patients with rare EGFR mutations remains uncertain.Therefore,it is urgent to clarify the significance of the relationship between EGFR rare mutation and clinicopathology,and to provide a reference for clinicians to formulate a treatment plan for EGFR rare mutation patients.Objective: In this paper,we collected rare cases of EGFR mutation and analyzed the significance of EGFR rare mutations and clinicopathological characteristics.Methods: From January 2013 to September 2017,the tumor samples of 1496 NSCLC patients were detected for EGFR gene mutations in the First Hospital of Jilin University,using amplification refractory mutation system(ARMS).The specimens used for EGFR mutation detection are paraffin embedded specimens,including surgical specimens,biopsy specimens,and specimen types from pleural effusion.The subtypes of adenocarcinoma tissues were determined by HE staining in 37 cases of EGFR rare mutations.Statistical analysis was carried out using SPSS 20.0 software,analysis of the differences between groups using χ2 test,P < 0.05 was statistically significant.Results: Of the 1496 patients,731(48.9%)had EGFR mutations,EGFR mutation was significantly more common in female than male patients(57.2% VS 39.1%,P < 0.001),more common in patients with no smoking than smoking patients(58.5% VS 30.2%,P < 0.001),more common in the adenocarcinoma than nonadenocarcinoma(53.4% VS 16%,P < 0.001);731 patients with EGFR mutations,including common EGFR mutations(19del,21L858R)in 625 cases,accounting for 85.5% of the EGFR mutations,the mutation rate of exon 19 del was 40.1%(293/731),the mutation rate of exon 21 L858 R was 45.4%(332/731);The number of rare EGFR mutation was 106,accounting for 14.5% of the EGFR mutation(37 male,69 female);There were 66 patients with single rare mutations: 18G719 X mutation,21L861 Q mutation,20S768 I mutation and insertion in exon 20 mutations were 26(24.5%),20(18.9%),6(5.7%)and 14(13.2%);The others were 40 patients with complex mutions(37.7%): G719X+L861Q(1),G719X+S768I(6),G719X+T790M(2),19del+ T790M(6),19del+L858R(8),S768I+L858R(4),T790M+L858R(9),L858R+L861Q(4).Rare EGFR mutations were common in women,non smoking,and adenocarcinoma,and rare EGFR mutations and common mutations were similar in clinicopathological features(P>0.05).The single rare mutations and complex mutations were similar in clinicopathological features(P>0.05).In 37 surgical specimens with rare mutations in EGFR,rare mutations in EGFR were found to be distributed differently in NSCLC tumors and in different subtypes of adenocarcinoma tissues.Conclusions:(1)EGFR mutations are highly prevalent in women,non-smoking and adenocarcinoma patients;(2)The rare mutations accounted for 14.5% of the EGFR mutation;(3)Rare EGFR mutations were more common in women,nonsmoking and adenocarcinoma,the comparison of common and rare mutations in EGFR was found to be similar to the clinicopathological features;(4)Rare mutations in EGFR are heterogeneous in tumor focus and adenocarcinoma subtype of NSCLC.