1187P - The role of mutations of EGFR, K-RAS, EML4-ALK, and B-RAF genes in resected pathological stage I lung adenocarcinoma

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Biomarkers
Non-Small-Cell Lung Cancer, Early Stage
Presenter Gouji Toyokawa
Authors G. Toyokawa1, T. Ohba1, K. Sugio2, Y. Morodomi3, T. Takenaka4, M. Yamaguchi3, F. Hirai3, K. Taguchi5, T. Seto3, Y. Ichinose6
  • 1Thoracic Oncology Dept., National Kyushu Cancer Center, 811-1396 - Fukuoka/JP
  • 2Department Of Thoracic Oncology, Clinical Research Institute, National Kyushu Cancer Center, Fukuoka/JP
  • 3Department Of Thoracic Oncology, National Kyushu Cancer Center, 811-1396 - Fukuoka/JP
  • 4Department Of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka/JP
  • 5Clinical Research Center, National Kyushu Cancer Center, Fukuoka/JP
  • 6Clinical Research Institute, National Kyushu Cancer Center, Fukuoka/JP

Abstract

Background

The mutations of EGFR, K-ras, EML4-ALK and B-RAF genes are an early event during oncogenesis of NSCLC. This study retrospectively assessed the mutations of these genes and their clinical significance in resected adenocacinomas.

Methods

A total of 256 patients with resected stage I lung adenocarcinoma were retrospectively included in this study. The mutations of EGFR and K-ras were determined using PCR-based fragment analysis and direct sequencing. The EML4-ALK fusion gene was assayed by immunohistochemistry and multiplex RT-PCR. The mutation of B-RAF gene was determined using direct sequencing. The DFS for prognostic value and the OS for predictive value of treatment after recurrence were evaluated.

Results

In 256 tumors, the mutations of EGFR, K-ras, EML4-ALK, and B-RAF genes were detected in 114 (44.5%), 14 (5.5%), 7 (2.7%), and 3 (1.2%). One patient with the EML4-ALK fusion gene harbored the mutation of EGFR, and double mutations of EGFR and B-RAF were also observed in one patient. The incidence of EGFR mutations was significantly higher in females than males (41.2% vs. 54.4%, p < 0.05). The incidence of K-ras mutations was higher in males than females and older patients than younger patients (not significant). The EML4-ALK fusion gene was detected in younger patients (4.2 vs. 0%). The DFS and OS of K-ras mutant group were significantly inferior than those of EGFR mutant group, EML4-ALK fusion gene group, and wild-type group. Twenty-four of 41 patients with recurrent disease after surgery were treated by EGFR-TKI and 17 patients were treated by other cytotoxic agents. In the patients treated by EGFR-TKI, the MST in patients with EGFR mutation (n = 15) was 53.4 months, which was significantly superior than that in patients without EGFR mutation (n = 9) of 20.1 months. In patients treated by cytotoxic agents, there was no difference in OS between EGFR-mutation positive and negative groups. Six of 7 patients with EML4-ALK fusion gene are alive without recurrent disease. However, the evaluation of prognostic value of EML4-ALK and B-RAF was difficult because of the small number of patient with mutation.

Conclusion

In patients with stage I adenocarcinoma, the mutation of K-ras gene was a poor prognostic factor for recurrence, and the mutation of EGFR was a predictive factor for EGFR-TKI treatment after recurrence.

Disclosure

All authors have declared no conflicts of interest.