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Clinicopathologic characteristics and prognostic impact of atypical EGFR mutations in completely resected lung adenocarcinoma

  • Author Footnotes
    1 These authors contributed equally to this work.
    Yunlang She
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Shenghui Li
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Jiajun Deng
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Yijiu Ren
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Mengmeng Zhao
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Yifan Zhong
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Yiming He
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Qiankun Chen
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Deping Zhao
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Yuming Zhu
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Likun Hou
    Affiliations
    Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Chunyan Wu
    Affiliations
    Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Dong Xie
    Correspondence
    Corresponding author: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
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  • Chang Chen
    Correspondence
    Corresponding author: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
    Affiliations
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:October 30, 2022DOI:https://doi.org/10.1016/j.ejca.2022.09.033

      Highlights

      • Resected atypical and classical EGFR-mutated lung adenocarcinoma have similar DFS.
      • L861Q mutation is associated with the poorest DFS among atypical EGFR mutations.
      • Adjuvant chemotherapy couldn't benefit atypical EGFR-mutated lung adenocarcinoma.

      Abstract

      Introduction

      This study evaluated the clinicopathologic characteristics and prognostic impact of atypical epidermal growth factor receptor (EGFR) mutations in patients with completely resected lung adenocarcinoma (LUAD) and investigate whether adjuvant chemotherapy could benefit the survival outcomes for these subjects.

      Material and methods

      We retrospectively reviewed resected LUAD samples from 8437 patients and identified 5358 EGFR-mutated (EGFRm) cases. Of these, 4847 had classical mutations, while 511 had atypical mutations. For further survival analysis, propensity score matching, Kaplan–Meier curve, and Cox regression analyses were conducted.

      Results

      Of the 511 patients with atypical EGFRm LUAD, 131 patients had compound mutations. The frequency of exon 20 insertion (20-ins), G719X, L861Q, S768I, and de novo T790M were 30.3%, 32.7%, 21.9%, 9.2%, and 11.4%, respectively. These patients included a higher proportion of males than those with classical EGFRm LUAD. Between the 483 matched pairs of the classical and atypical EGFRm patients, no significant difference emerged in disease-free survival (DFS) (p = 0.476). Patients with the L861Q mutation had the poorest DFS among those with atypical EGFRm LUAD (p = 0.005). Cox regression analyses revealed that the L861Q mutation was an independent prognostic factor for DFS in 487 patients with solely atypical EGFRm LUAD. In addition, adjuvant chemotherapy did not improve the DFS for those patients, whether in stage IB (p = 0.638) or II-III (p = 0.505) of the disease.

      Conclusion

      The L861Q mutation is an independent prognostic factor for DFS in patients with atypical EGFRm LUAD after complete resection who would not benefit from adjuvant chemotherapy regardless of disease stage.

      Graphical abstract

      Keywords

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