Clinicopathologic characteristics of the EGFR gene mutation in non-small cell lung cancer

Background: The authors sought to define clinicopathologic features associated with mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC). Methods: The authors evaluated surgically resected NSCLC tumors for EGFR (exons 18-21) and KRAS (codons 12-13) mutations and immunohistochemistry (EGFR, phosphorylated-EGFR, and HER2/Neu), and correlated results with clinical outcome and patient and disease features. After their analysis on 159 patients was completed, they selected a second cohort of Asian patients (n = 22) and compared EGFR mutation results to place of birth and immigration to the United States. Results: Of 159 patients, 14 had EGFR mutations and 18 had KRAS mutations. EGFR mutations were associated with adenocarcinoma (p = 0.002), female gender (p = 0.02), never-smoking (p < 0.0001), Asian ethnicity (p = 0.005), air bronchograms (p = 0.004), and multiple wedge resections (p = 0.03). Although statistical significance was not reached, a higher incidence of synchronous primary cancers (36% versus 17%; p = 0.09) and a smaller median tumor size (11.8 cm(3) versus 24.0 cm(3); p = 0.24) were seen. There was no difference in disease-free survival; however, median overall survival in patients with EGFR mutations was shorter (3.49 versus 4.29 years; p = 0.85). EGFR mutation did not correlate with immunohistochemistry. In the second cohort of 22 Asian patients, 12 (55%) had the mutation. Of interest, there was no geographic difference in incidence of EGFR mutation. Asian women with the EGFR mutation developed adenocarcinoma at an earlier age than other lung cancer patients. Conclusion: There is a distinct clinical profile for NSCLC patients with the EGFR mutation. However, this mutation does not alter disease-free survival and is likely attributable to an inherited susceptibility instead of an environmental effect.