Study On Double Screening Of EGFR Mutation And FISH Detection For Sensitive Patients Using Erlotinib

?Background and Purpose?Lung cancer is one of the most common malignant tumors and its mortality is rated at the first in the world.Specially,Non-small cell lung cancer(NSCLC)accounts for over 80% of lung cancer and most of those patients are diagnosed as late stages disease [1,2].Chemotherapy and radiation have been used for patients with locally advanced or distant metastatic lung cancer,but their effect of overall treatment are not satisfactory.In recent years,molecular targeted therapy has become a hot topic in lung cancer treatment.Some studies have shown that EGFR-TKIs makes a significant efficacy on patients with EGFR sensitive mutations of advanced NSCLC,indicating that EGFR gene mutation state is one of important predictive factors for EGFR-TKIs treatment[15-17].20%-30% of NSCLC patients with EGFR sensitive mutations are poor response or inefficacy from EGFR-TKIs treatment whereas only 70%-80% are effectivity and its efficacy was visible differences[5-7].Some studies have shown that EGFR gene amplification is also a curative effect factor in EGFR-TKIs treatment.Patients with high EGFR gene amplification copy numbers are likely to benefit more from EGFR-TKIs treatment than those of low[13-15].Therefore,it is speculated that patients with EGFR sensitive mutations with EGFR gene amplification may be benefited more than those without EGFR gene amplification in EGFR-TKIs treatment.The trend has been found in previous retrospective studies,but it needs to confirm by prospective studies.In this research,we are according as EGFR gene mutation and gene amplification copy numbers of NSCLC patients to divided into FISH-positive group and FISH-negative group.The purpose of prospective study conducts to different efficacy of erlotinib treatment in FISH-positive and FISH-negative groups.?Method?1.Apply ARMS method to detect NSCLC patient's EGFR gene mutation during the III or IV inoperable pathological stages,which screening experimental subjects with EGFR 19 exon mutation or EGFR 21 exon(L858R)mutation.2.The FISH method was used to detect EGFR gene amplification copy numbers of experimental patients.According to the results,we divided the patients into FISH-positive group and negative group.(P.S.4 or more EGFR signal nucleus ratio is equal or over 40% was defined the FISH-positive)3.Receive erlotinib(150mg/day)treatment until disease progression or intolerable side effects,follow-up the progression-free survival and overall survival in all experimental patients.4.Analyzed by Statistics software SPSS 20.0 from research data.Significant analysis was performed by chi-squared test and t-test;survival analysis was performed by log-rank test and Kaplan-Meier model;multivariate correlation analysis was performed by logistic regression analysis and linear correlation analysis;there is significance analysis to P<0.05.?Result?1.The whole median PFS in two group is 10 months.The median PFS is 10.5 months and its ORR is 66.7% in FISH-positive group while the median PFS is 7 months and its ORR is 60.0% in FISH-negative group.There is no statistical significance in median PFS and ORR between two groups(P = 0.1212 and X2 = 0.196,P = 0.6610).2.The median PFS is 10 months and its ORR is 70.8% from EGFR19 exon mutation patients group,whereas the median PFS from EGFR21 exon mutation group is 10 months and its ORR is 57.1%.There is no statistical significance in median PFS and ORR between two groups(P = 0.1168 and X2 = 0.916,P = 0.3380).3.The median PFS in FISH-positive group with EGFR 19 exon mutation and EGFR 21 exon mutation are 14 months and 9 months respectively,whose median PFS has statistical significance(P = 0.0074).4.The median PFS from EGFR 19 exon mutation group between FISH-positive patients group and FISH-negative group are 14 months and 5 months respectively,whose median PFS has statistical significance.(P = 0.0045).5.It is found that there is a linear correlation between the PFS and EGFR gene am-plification copy numbers in FISH-positivegroup(r2=0.1665,P=0.0252,K=-0.8904).?Conclusion?The median PFS in positive group with EGFR 19 exon mutation and EGFR gene amplification copy numbers is more advantage than those without EGFR gene amplification when patients adopt erlotinib treatment.Hence,the double molecular markers combined ARMS method detected EGFR mutation state with FISH method detected EGFR gene amplification state may be more efficient screening for sensitive patients of erlotinib.