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Mutations of the EGFR, K-ras, EML4–ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma

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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.

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Abbreviations

EGFR:

Epidermal growth factor receptor

EML4–ALK:

Echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase

BRAF:

v-raf murine sarcoma viral oncogene homolog B1

TKI:

Tyrosine kinase inhibitor

DFS:

Disease-free survival

OS:

Overall survival

PFS:

Progression-free survival

NSCLC:

Non-small cell lung cancer

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Acknowledgments

We thank Miss Yumiko Oshima for reviewing the patients’ charts. This study was supported in part by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science, and a grant from the Uehara Memorial Foundation.

Author information

Authors and Affiliations

  1. Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan

    Taro Ohba, Gouji Toyokawa, Atsushi Osoegawa, Fumihiko Hirai, Masafumi Yamaguchi, Takashi Seto, Mitsuhiro Takenoyama & Kenji Sugio

  2. Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan

    Yukito Ichinose & Kenji Sugio

  3. Cancer Pathology Laboratory, National Kyushu Cancer Center, Fukuoka, Japan

    Ken-ichi Taguchi

  4. Department of Thoracic and Breast Surgery, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

    Atsushi Osoegawa & Kenji Sugio

Authors
  1. Taro Ohba
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  2. Gouji Toyokawa
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  3. Atsushi Osoegawa
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  4. Fumihiko Hirai
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Corresponding author

Correspondence to Kenji Sugio.

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Ohba, T., Toyokawa, G., Osoegawa, A. et al. Mutations of the EGFR, K-ras, EML4–ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma. Surg Today 46, 1091–1098 (2016). https://doi.org/10.1007/s00595-015-1295-z

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  • DOI: https://doi.org/10.1007/s00595-015-1295-z

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