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The mutations of the EGFR and K-ras genes in resected stage I lung adenocarcinoma and their clinical significance
Authors:Taro Ohba  Gouji Toyokawa  Takuro Kometani  Kaname Nosaki  Fumihiko Hirai  Masafumi Yamaguchi  Motoharu Hamatake  Takashi Seto  Yukito Ichinose  Kenji Sugio
Affiliation:1. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan
2. Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan
3. Department of Thoracic and Breast Surgery, Oita University, Yufu, Japan
Abstract:

Purpose

This study retrospectively assessed the mutations of the epidermal growth factor receptor (EGFR) and K-ras genes and their clinical significance in patients with resected stage I adenocarcinomas.

Methods

A total of 354 patients with resected lung adenocarcinomas were included, and 256 patients with stage I disease were analyzed for the prognostic and predictive value of these mutations.

Results

Mutations of EGFR and K-ras genes were detected in 149 (41.1 %) and 23 (6.4 %) of all tumors, and in 122 (47.6 %) and 14 (5.5 %) of stage I tumors, respectively. There were no significant differences in the disease-free survival (DFS) and overall survival (OS) between the EGFR-mutant and wild-type groups. However, the DFS and OS were significantly shorter in patients with K-ras mutations than in those without (5-year DFS: 50.8 vs. 76.9 %, 5-year OS: 70.0 vs. 86.6 %, p < 0.01). A multivariate analysis showed that K-ras mutations were an independent poor prognostic factor. Twenty-four of the 41 patients with recurrent disease after surgery were treated with an EGFR–TKI. Fifteen EGFR-mutant patients treated with an EGFR–TKI had a better prognosis than did the nine EGFR-wild-type patients.

Conclusion

The presence of an EGFR gene mutation was a predictive factor for the response to EGFR–TKI treatment in patients with resected stage I adenocarcinoma, but was not a prognostic factor. The presence of a K-ras gene mutation was a poor prognostic factor.
Keywords:
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