Abstract A155: Mutations of the EGFR, K-ras, and EML-4ALK genes in resected stage I lung adenocarcinoma and their clinical significance.
Authors: Ohba Taro , Sugio Kenji , Toyokawa Gouji , Hirai Fumihiko , Yamaguchi Masafumi , Maruyama Riichiroh , Hamatake Motoharu , Seto Takashi , Ichinose Yukito 
Published: June 2012

Background: Mutations of the epidermal growth factor receptor (EGFR), K-ras and echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) genes are an early event during the oncogenesis of non-small lung cancer (NSCLC). This study retrospectively assessed the mutations of the EGFR, K-ras, and EML4-ALK genes and their clinical significance in patients with resected stage I lung adenocacinomas.

Methods: A total of 256 patients with resected stage I lung adenocarcinomas were retrospectively included in the study. The mutations of the EGFR (exons 19 and 21) and K-ras (codons 12 and 13) were determined using a PCR-based fragment analysis and sequencing, and the inversion of EML4-ALK was examined using multiplex RT-PCR. The disease-free survival (DFS) and the overall survival (OS) were evaluated to determine the prognostic and predictive values of treatment after recurrence.

Results: Mutations of the EGFR and K-ras genes were detected in 122 (47.6%) and 14 (5.5%) of the 256 tumors, respectively. The inversion of EML4-ALK was detected in 2 (3.9%) of the 51 tumors examined. The incidence of EGFR mutations was significantly higher in females than in males (54.4% vs. 41.2%, p&lt;0.05). There were no significant differences in the DFS and OS between the patients with wild-type and mutant EGFR. The 5-year DFS and OS in the K-ras mutation group were significantly inferior to those in the K-ras wild-type group (DFS; 50.0% vs. 76.9%, OS; 70.7 vs. 83.4%, p&lt;0.01). Twenty-four of the 41 patients with recurrent disease after surgery were treated with an EGFR-TKI, such as gefitinib or erlotinib, and 17 patients were treated with other anticancer drugs. The patients with an EGFR mutation treated with an EGFR-TKI (n=14) had a better prognosis than the patients without an EGFR mutation (n=10; MST after recurrence: 54.3 vs. 21.1 months, p&lt;0.01). There were no differences in the OS between the EGFR mutation positive and negative groups treated without an EGFR-TKI. K-ras mutations were not associated with the OS. The two patients with inversion of EML4-ALK did not have recurrent disease, and were still alive over 5 years after the diagnosis, however, the evaluation of the prognostic value of the inversion was not possible because of the small number of patients who had the inversion.

Conclusion: The presence of a mutation of the K-ras gene was a poor prognostic factor for recurrence after surgery in patients with stage I adenocarcinoma of the lung who underwent surgery. The presence of a mutation of the EGFR gene was a predictive factor for a response to EGFR-TKI treatment in patients after recurrence.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A155.