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Prognostic value of KRAS mutations, TP53 mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy
  1. Ea Maria Tønning Tønnesen1,2,
  2. Magnus Stougaard1,3,
  3. Peter Meldgaard3,4,
  4. Johanne Lade-Keller1,3
  1. 1Department of Pathology, Aarhus University Hospital, Aarhus, Denmark
  2. 2Department of Pathology, Viborg Regional Hospital, Viborg, Denmark
  3. 3Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  4. 4Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
  1. Correspondence to Dr Ea Maria Tønning Tønnesen, Department of Pathology, Aarhus University Hospital, Aarhus N, Denmark; Ea{at}


Aims The aim of this study was to investigate the association between oncogenic alterations and programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinomas, as well as the prognostic value of KRAS and/or TP53 mutations in patients treated with immunotherapy.

Methods This study is a retrospective cohort study of 519 patients with lung adenocarcinomas analysed for mutations and PD-L1 expression. Data were collected from electronic pathology record system, next-generation sequencing system, and clinical databases. Association between mutations and PD-L1 expression was investigated, as well as survival statistics of the 65 patients treated with immunotherapy.

Results 41% of the samples contained a KRAS mutation, predominantly together with mutations in TP53 (41%) or STK11 (10%). Higher expression of PD-L1 was seen among patients with KRAS mutations (p=0.002) and EGFR wild type (p=0.006). For patients treated with immunotherapy, there was no statistically significant difference for overall survival (OS) and progression-free survival (PFS) according to KRAS mutation status, TP53 mutation status or PD-L1 expression. The HR for concomitant mutations in TP53 and KRAS was 0.78 (95% CI 0.62 to 0.99) for OS and 0.43 (0.21 to 0.88) for PFS. Furthermore, concomitant TP53 and KRAS mutations predicted a better PFS (p=0.015) and OS (p=0.029) compared with no mutations or a single mutation in either TP53 or KRAS.

Conclusion Mutations in TP53 together with KRAS may serve as a potential biomarker for survival benefits with immunotherapy.

  • Lung Neoplasms
  • Antibodies, Monoclonal
  • Pathology Department, Hospital

Data availability statement

Data are available on reasonable request.

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  • Handling editor Runjan Chetty.

  • Contributors Responsible for overall content: JL-K. Responsible for concept and design: JL-K and MS. Data collection: EMTT, JL-K, MS and PM. Performed the statistical analysis: EMTT. Interpretation of the data: EMTT, JL-K, MS and PM. Writing: EMTT, JL-K, MS and PM. The manuscript was approved by all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.