Taro Ohba1, Gouji Toyokawa1, Atsushi Osoegawa1,2, Fumihiko Hirai1, Masafumi Yamaguchi1, Ken-Ichi Taguchi3, Takashi Seto1, Mitsuhiro Takenoyama1, Yukito Ichinose4, Kenji Sugio5,6,7. 1. Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan. 2. Department of Thoracic and Breast Surgery, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan. 3. Cancer Pathology Laboratory, National Kyushu Cancer Center, Fukuoka, Japan. 4. Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan. 5. Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan. ksugio@oita-u.ac.jp. 6. Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan. ksugio@oita-u.ac.jp. 7. Department of Thoracic and Breast Surgery, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan. ksugio@oita-u.ac.jp.
Abstract
BACKGROUND AND PURPOSE: The EGFR, K-ras, EML4-ALK, and BRAF genes are oncogenic drivers of lung adenocarcinoma. We conducted this study to analyze the mutations of these genes in stage I adenocarcinoma. METHODS: The subjects of this retrospective study were 256 patients with resected stage I lung adenocarcinoma. We analyzed mutations of the EGFR, K-ras, and BRAF genes, and the EML4-ALK fusion gene. We also assessed disease-free survival (DFS) to evaluate the prognostic value and overall survival (OS) to evaluate the predictive value of treatment after recurrence. RESULTS: Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes were detected in 120 (46.8 %), 14 (5.5 %), 6 (2.3 %), and 2 (0.8 %) of the 256 tumors. Two tumors had double mutations (0.8 %). The incidence of EGFR mutations was significantly higher in women than in men. The EML4-ALK fusion gene was detected only in younger patients. The DFS and OS of the K-ras mutant group were significantly worse than those of the EGFR mutant group, the EML4-ALK fusion gene group, and the wild-type group. Six of the seven patients with the EML4-ALK fusion gene are still alive without recurrent disease. CONCLUSIONS: In patients with stage I adenocarcinoma, mutation of the K-ras gene was a poor prognostic factor for recurrence. The presence of a mutation of the EGFR or EML4-ALK gene was not a prognostic factor.
BACKGROUND AND PURPOSE: The EGFR, K-ras, EML4-ALK, and BRAF genes are oncogenic drivers of lung adenocarcinoma. We conducted this study to analyze the mutations of these genes in stage I adenocarcinoma. METHODS: The subjects of this retrospective study were 256 patients with resected stage I lung adenocarcinoma. We analyzed mutations of the EGFR, K-ras, and BRAF genes, and the EML4-ALK fusion gene. We also assessed disease-free survival (DFS) to evaluate the prognostic value and overall survival (OS) to evaluate the predictive value of treatment after recurrence. RESULTS: Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes were detected in 120 (46.8 %), 14 (5.5 %), 6 (2.3 %), and 2 (0.8 %) of the 256 tumors. Two tumors had double mutations (0.8 %). The incidence of EGFR mutations was significantly higher in women than in men. The EML4-ALK fusion gene was detected only in younger patients. The DFS and OS of the K-ras mutant group were significantly worse than those of the EGFR mutant group, the EML4-ALK fusion gene group, and the wild-type group. Six of the seven patients with the EML4-ALK fusion gene are still alive without recurrent disease. CONCLUSIONS: In patients with stage I adenocarcinoma, mutation of the K-ras gene was a poor prognostic factor for recurrence. The presence of a mutation of the EGFR or EML4-ALK gene was not a prognostic factor.
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