Mutations of EGFR, K-ras, and EML-4ALK genes in resected lung adenocarcinoma and their clinical significance.

Abstract

7033 Background: Mutations of EGFR, K-ras and EML4-ALK are an early event during oncogenesis of NSCLC. This study retrospectively assessed the mutations of EGFR, K-ras, and EML4-ALK and their clinical significance in resected adenocacinomas. Methods: A total of 354 patients with resected lung adenocarcinomas were retrospectively included. The mutations of EGFR (exons 19 and 21) and K-ras were determined using PCR-based fragment analysis and sequencing, and the inversion of EML4-ALK was examined using multiplex RT-PCR. The DFS for the prognostic value and the OS for the predictive value of treatment after recurrence were evaluated. Results: Mutations of EGFR and K-ras were detected in 149 (41.1%) and 18 (5.1%) of 354 tumors, respectively. The inversion of EML4-ALK was detected in 6 (7.5%) of 80 tumors. The incidence of EGFR mutations was significantly higher in females than males (52% vs. 33%, p<0.01), and in non-smokers than smokers (50% vs. 34%, p<0.01). There was no significant difference in the DFS between the mutation and wild-type groups in EGFR and K-ras. The median DFS in K-ras mutant group was 25 months which was inferior to that in EGFR-mutant group (not reached). The OS was significantly longer in pts with EGFR-mutations than in pts without EGFR-mutation (5-year survival: 82.8% vs. 67.1%, p<0.01). Fifty-six of 102 pts with recurrent disease after surgery were treated with EGFR-TKI and 46 pts were treated with other anticancer drugs. The EGFR-mutant pts (n=32) treated with EGFR-TKI had better prognosis than the EGFR-wild pts (n=24; MST after recurrence: 53 vs. 27 months, p<0.001). There was no difference in OS between EGFR mutation positive and negative groups treated without EGFR-TKI. K-ras mutations were not associated with OS. Three of 6 pts with inversion of EML4-ALK had recurrent disease and were still alive with treatment, however, the evaluation of the prognostic value was difficult because of the small number of pts with inversion. Conclusions: The mutation of EGFR was not a prognostic factor but was a predictive factor for EGFR-TKI treatment in pts with adenocarcinoma of the lung that underwent surgery. The mutation of K-ras might be poor prognostic factor.