Epidermal Growth Factor Receptor Gene Mutation Status Is Associated With Clinical Characteristics, Chemotherapy Effect And The Outcome Of Non-small Cell Lung Cancer

Objective: Lung cancer is one of the diseases that threaten human health,its morbidity and mortality located on the first of the world malignant tumor,inwhich non-small cell lung cancer (NSCLC) accounts for more than80%,because of the incidence of occult nonspecific symptoms,most of thepatients are locally advanced or late diagnosis, if you do not take the treatment,the one year survival rate of less than10%.Recently, with the cognition of themolecular mechanisms of lung cancer,the targeted drugs for the epidermalgrowth factor receptor(EGFR) become a hotspot of non-small cell lung cancer.EGFR is one of the erB/HER family,also a transmembrane protein. Blockingthe signal transduction pathway is a main target for non-small cell lungcancer.At present, a large number of studies have shown that EGFR mutationsis a predictor in the tyrosine kinase inhibitors (tyrosine kinase inhibitors, TKI)efficacy.This study is aim to research the EGFR gene19,21exon mutationstatus,and the relationship between EGFR and clinical characteristics,treatment efficacy and survival of NSCLC patients.Then,to provide theclinical basis for the individualized treatment and prognosis.Methods: The73cases of NSCLC patients were collected that werehospitalized in the respiratory department of the Fourth Hospital from March2011to June2012,which confirmed by histopathology.According to therequirements,we record the clinical information for all patients, includinggender, age, smoking status, histological type, clinical staging, treatment andefficacy.To exam the exon19and21by direct sequencing method or ARMSmethod,and analyze the relationship between EGFR and clinicalfeatures,treatment efficacy and survival.By SPSS13.0statistical analysissoftware χ2test, Fisher exact test, as well as rank-sum test,to analyze the rate.The survival rates and survival curves are evaluated by the Kaplan-Meiermethod,and compared by the Log-Rank test. All statistical results of P <0.05is considered statistically significant.Results:1All study subjects,male accounted for47.9%(n=35),female accounted for52.1%(38cases),the mean age of59.14+/-11.31years.Less than60wereaccounted for61.6%(45cases),>60years old accounted for38.4%(28cases);adenocarcinoma accounted for87.7%(64cases),squamous cellcarcinomas accounted for12.3%(9cases);Smokers accounted for30.1%(22cases),non-smokers accounted for69.9%(51cases); TNM stageⅢ accounted for13.7%(10cases),stage Ⅳaccounted for86.3%(63cases);patients with direct sequencing methodaccounted for47.9%(35cases),patientswith PCR-ARMS method,accounted for52.1%(38cases); source of specimens:primary foci specimens was57.6%（42/73）,which consist of threeportions:lung biopsy specimens was43.8%(32/73), fiberoptic bronchoscopybite test specimens was6.8%(5/73),postoperative histopathological specimenswas6.8%(5/73); metastatic supraclavicular lymph nodes biopsy specimenswas34.2%(25/73), and the way other sources accounted for8.2%(6/73).2Our study had completed73cases of patients with NSCLC EGFR genemutation detection,accounting for58.4%in patients treated first (73/125).EGFR mutation occurred in58.9%(43/73)of our NSCLC cases,of which,21cases located at exon19,15acses located at the exon21,7cases located atexon19and21.Moreover,there are30cases not occurred,accounting for41.1%(30/73).3The EGFR mutation rate was significantly higher in females(71.1%) thanin males(45.7%).The muatation rate was significantly higher inadenocarcinoma(65.6%) than squama(11.1%).The mutation rate wassignificantly higher in non-smoker patients (70.6%) than smokers（31.8%）.However, no statistically significance correlation was foundbetween the mutation and patients’ age (55.6%vs64.3%),TNM stage(50.0%vs60.3%), primary foci and metastatic supraclavicular lymph nodes (69.0%vs56.0%),detecting method(62.9%55.3%).437patients were able to evaluate the efficacy of4cycles ofchemotherapy,of which14cases EGFR mutated,23cases wide-type.Mutatedobjective response (ORR)and disease control rates (DCR)were7.1%and64.3%respectively; ORR and DCR wild-type patients were13.0%and78.3%respectively. there was no statistically significant difference between the twogroups about the ORR(P=0.509) and DCR(P=0.290).5The PFS (progression-free survival) in patients with oral EGFR-TKI wassignificantly higher in EGFR mutated than in wide-type.6In57cases with NSCLC that had accurate survival data,33cases withEGFR mutated and24cases with wide-type. The median survival time intwo groups were15months (95%CI,7.0-23.0months) and18months (95%CI,13.4-22.6months)respectively.1year survival rates were60.6%(20/33)and75.0%(18/24), no difference between the survival and the two groups.Conclusions:1Our study had completed73cases of patients with NSCLC EGFR genemutation detection,accounting for58.4%in patients treated first (73/125).EGFR mutation occurred in58.9%，of which exon19mutation rate is48.8%,exon21mutation rate is34.9%,exon19,21mutation rate is16.3%.2EGFR gene mutation rate is hign in females,adenocarcinoma,non-smokersthan the others.No statistically significance correlation was found between theEGFR gene mutation and patients’age,TNM stage, primary foci and metastaticsupraclavicular lymph nodes,detecting method.3EGFR gene mutation is a predictor of molecular targeted drug efficacy,butit can not be a predictor of a platinum-based third generation chemotherapydrug efficacy.4EGFR gene mutation is not as an independent predictor of survival ofnon-small cell lung cancer.