Value Of The Epidermal Growth Factor Receptor Mutation Status For Predicting The Prognosis Of Non-Small-Cell Lung Cancer Patients

ObjectivesPrimary lung cancer is the leading cause of cancer death worldwild. Epidermal growth factor receptor (EGFR) specific Tyrosine kinase inhibitors (TKIs) were widely used as molecularly targeted drugs for Non-Small-Cell Lung Cancer (NSCLC). Mutations in the EGFR tyrosine kinase domain have been studied in relation to the response to EGFR inhibitors, while the relationship between EGFR mutation status and clinicopathological factors,and the mutation on the effect in non-small cell lung cancer (NSCLC) treated with surgery has not yet been reported. The aim of the present study was to investigate the relationship between EGFR mutation status and clinicopathological factors, and to analyze the effect on NSCLC after surgery.MethodsLung cancer patients who received potential curative surgery and screened for EGFR gene mutation status from March2009to March2011was retrospectively reviewed. Mutation spacific quatitiative PCR was used to detect the EGFR gene mutations status and immunohistochemistry was used to detect ERCC1protein expression and four Tumor Markers (TMs) that were NSE, CEA, SCC and Cyfra21-1. The aim of the present study was to analyze the relationship between EGFR mutation status and clinicopathological factors, ERCC1, tumor markers and prognostic.Results1. The mutation group and the wild has159and214patients respectively. The frequency of EGFR mutations, which were mainly located in exon19(49.7%) and exon21(47.9%) was33%. ERCC1expression was detected in tumors tissue from293patients (39.2%).2. EGFR mutation in female, non-smoking, adenocarcinoma and less than60years old accounted for64.8%,61.6%,89.3%and62.9%with statistical significance compared with male (p=0.000,χ2=54.185), smoking (p=0.000, x2=47.337), non-adenocarcinoma (p=0.000,χ2=110.295) and more than60years old (p=0.010, χ2=6.585). In addition, there were some relations between mutation status and ERCC1protein, T stage, the metastatic lymph node ratio (LNR). ERCCl(-)(X2=6.635, p=0.010), T1-2, LNR=18%is common in mutation group.3. In addition,there are some relations between mutation status and CEA, SCC and Cyfra21-1. SCC (p=0.000, χ2=15.092) and Cyfra21-1(p=0.009, χ2=6.902) more than normal value is common in wild group. Increased CEA was common in mutation group (p=0.023, χ2=5.135)4. Disease free survival (DFS) of the wild group better than mutation group (χ2=10.247,p=0.001). In the univariate analysis, the non-smoking, pathological type, TNM stage, LNR, CEA, Cyfra21-1and NSE played important roles in predicting overall survival (OS)(p<0.001) by Kaplan-Meier survival analysis. In the multivariate analysis, pathological type and TNM stage were independent prognostic factors for OS [hazard ratio (HR)1.458,95%confidence interval (CI)1.067～1.992, p=0.018and hazard ratio (HR)1.599,95%confidence interval (CI)1.018～2.511,p=0.042, respectively]. Clinicopathological factors, Ⅰ～Ⅱ stage, low-LNR and CEA in normal value was also significantly associated with better DFS (p<0.05).Conclusions1. EGFR mutation was commonly found in female, non-smoking, adenocarcinoma and patients less than60years old. EGFR mutations were more frequently found in ERCC1-negative tumors, and high-LNR were more frequently found in EGFR mutated group.2. Tumor markers may predict the mutation status, which need further research.3. The wild-type group confers better DFS than mutation patients. The non-smoking, pathological type, TNM stage, LNR, CEA, Cyfra21-1and NSE played an important role in predicting OS. Pathological type and TNM stage was an independent prognostic factor for OS.