Clinical Characteristics And Prognosis Of Lung Cancer Patients With EGFR Mutations In Exons 19 And 21

Background and objective Studies on the epidermal growth factor receptor(EGFR) signaling pathways and the therapeutic effects of EGFR-tyrosine kinase inhibitors(EGFR-TKIs) have recently proven that targeted therapy has a major role in the treatment of lung cancer. However, recently studies indicate that the therapeutic effects of EGFR-TKIs on lung cancers with different EGFR mutation subtypes are different, and the reason still remains unclear. The aim of this study is first to investigate the clinical characteristics of lung cancer patients with EGFR mutations in exons 19, 21, to compare the outcomes of these patients between exon 19 mutations and exon 21 mutations. We also detected the complex mutations of EGFR in these patients and analyzed the correlation between these mutations with the patients’ clinic characteristics.Methods The study recruited 113 patients who had non-small cell lung cancer(NSCLC) with EGFR mutations. EGFR mutations were detected for 47 patients using Real-time PCR plus DNA sequencing. The mutations of the remaining patients were determined using x Tag-EGFR liquid chip technology. All of 8 patients with complex mutations were detected via Real-time PCR plus DNA sequencing. All stages I-III patients underwent radical resection followed by 4 cycles of postoperative chemotherapy. Patients with pleural metastases underwent pleural biopsy, pleurodesis, and chemotherapy only. Patients with distant metastases underwent biopsy and chemotherapy only. Collected clinical data were analyzed using SPSS 19.0 software.Results EGFR mutations in exons 19 and 21 were found in 56 and 57 patients, respectively. The mean age of patients with exon 19 mutations was lower than the age of the patients with exon 21 mutations(57.02±11.31 years vs 62.25±7.76 years, respectively; P<0.05). The primary tumors of patients with exon 19 mutations were more likely occur in the right lung. There were no significant differences in gender, smoking status, histopathology, level of differentiation, and stage of disease(P>0.05) between the patients with exon 19 and 21 mutations; and survival analysis of 91(80.5%, 91/113) patients with complete clinical data found no differences in overall survival. In the group of patients with age>61 years, male gender, ever smoking, and stage IV disease, stratification analysis found out that patients with exon 19 mutations had longer overall survival compared to the patients with exon 21 mutations, although the differences were not statistically significant. At the same time, we also found 8 patients with EGFR complex mutations. In these 8 patients, 3 of cases with EGFR complex mutations contain L858 R mutation. The primary tumors of patients with L858 R plus other mutations were more likely occur in the left lung(P=0.028). There were no significant differences in age, gender, smoking status and histopathology(P>0.05) between the EGFR complex mutations patients with and without L858 R mutations. Patients with L858 R plus other mutations present a greater malignant behavior compared to the EGFR complex patients without L858 R mutation via survival analysis, although the differences were not statistically significant.Conclusion Compared to the lung cancer patients with EGFR exon 21 mutations, the patients with EGFR exon 19 mutations were younger, and their primary tumors were more likely to occur in the right lung. There were no significant differences between the lung cancer patients with exon 19 and 21 mutations for overall survival, gender, smoking status, histopathology, level of differentiation, and disease stage. In terms of EGFR complex mutations, the patients with L858 R mutation present a greater malignant behavior in comparison with the rest of patients with EGFR complex mutations, and their primary tumors were more likely occur in the left lung. There were no significant differences in age, gender, smoking status and histopathology between the EGFR complex mutations patients with and without L858 R mutations. However, as lack of samples in this study, sufficient clinical data and further investigations were required to affirm these perspectives.