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Caveolin-1 expression predicts favourable outcome and correlates with PDGFRA mutations in gastrointestinal stromal tumours (GISTs)
  1. Luca Bertero1,
  2. Alessandro Gambella1,
  3. Antonella Barreca2,
  4. Simona Osella-Abate3,
  5. Luigi Chiusa2,
  6. Paola Francia di Celle3,
  7. Patrizia Lista4,
  8. Mauro Papotti5,
  9. Paola Cassoni1
  1. 1Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
  2. 2Pathology Unit, "Città della Salute e della Scienza di Torino" University Hospital, Turin, Italy
  3. 3Molecular Pathology Unit, "Città della Salute e della Scienza di Torino" University Hospital, Turin, Italy
  4. 4Oncology Unit, "Città della Salute e della Scienza di Torino" University Hospital, Turin, Italy
  5. 5Pathology Unit, Department of Oncology, University of Turin, Turin, Italy
  1. Correspondence to Professor Paola Cassoni, Department of Medical Sciences, University of Turin, Via Santena 7, Torino 10126, Italy; paola.cassoni{at}unito.it

Abstract

Aims Novel prognostic markers are warranted for gastrointestinal stromal tumours. Caveolin-1 is a multifunctional protein that proved to be associated with outcome in multiple tumour types. Aim of this study was to investigate Caveolin-1 expression and prognostic efficacy in a series of gastrointestinal stromal tumours.

Methods Caveolin-1 expression was assessed by immunohistochemistry in a retrospective series of 66 gastrointestinal stromal tumours representative of the different molecular subtypes. Correlations with clinical, histopathological and molecular features were investigated. Statistical analyses were performed as appropriate.

Results Thirty-five cases out of 66 (53.0%) expressed Caveolin-1. Presence of Caveolin-1 expression correlated with favourable histopathologic and clinical traits, including a lower mitotic count (p=0.003) and lower relapse rate (p=0.005). Caveolin-1 expression also resulted associated with the presence of PDGFRA mutations (p=0.010). Outcome analyses showed a favourable prognostic significance of Caveolin-1 expression in terms of relapse-free survival (HR=0.14; 95% CI=0.03 to 0.63) and overall survival (HR=0.29; 95% CI=0.11 to 0.74), even after adjusting for the mutational subgroup (relapse-free survival: HR=0.14, 95% CI=0.04 to 0.44; overall survival: HR=0.29, 95% CI=0.11 to 0.51) and imatinib treatment (relapse-free survival: HR=0.14, 95% CI=0.02 to 0.81; overall survival: HR=0.29, 95% CI=0.17 to 0.48).

Conclusion Caveolin-1 represents a novel prognostic marker in gastrointestinal stromal tumours. Further studies are warranted to validate these results and to explore the mechanisms linking Caveolin-1 expression with the PDGFRA oncogenic pathway.

  • pathology
  • molecular
  • gastrointestinal neoplasms
  • immunohistochemistry

Data availability statement

Data supporting the findings of the present study are not publicly available due to privacy/ethical restrictions, but can be obtained from the corresponding author upon reasonable request.

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Data availability statement

Data supporting the findings of the present study are not publicly available due to privacy/ethical restrictions, but can be obtained from the corresponding author upon reasonable request.

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Footnotes

  • LB and AG are joint first authors.

  • Handling editor Runjan Chetty.

  • Twitter @AleKuma90

  • Contributors Study design: LB and PC; data curation: LB and AG; formal analysis: LB, AG, AB, SO-A and PFdC; investigation: LB, AG, AB, SO-A and PFdC; methodology: LB; validation: PC; writing—original draft: LB and AG; writing—review and editing: LB, AG, AB, SO-A, LC, PFdC, PL, MP and PC. All the contributing authors have read and approved the manuscript.

  • Funding This work was supported by the Italian Ministry for Education, University and Research (Ministero dell'Istruzione, dell'Università e della Ricerca—MIUR) under the program 'Dipartimenti di Eccellenza 2018–2022' (grant number D15D18000410001).

  • 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.

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