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  • Overexpression of integrin alpha 2 (ITGA2) correlates with poor survival in patients with pancreatic ductal adenocarcinoma

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Original research
Overexpression of integrin alpha 2 (ITGA2) correlates with poor survival in patients with pancreatic ductal adenocarcinoma
  1. Steffen Deichmann1,
  2. Leif Schindel1,
  3. Rüdiger Braun1,
  4. Louisa Bolm1,
  5. Martin Taylor2,
  6. Vikram Deshpande2,
  7. Oliver Schilling3,
  8. Peter Bronsert3,4,
  9. Tobias Keck1,
  10. Cristina Ferrone5,
  11. Ulrich Wellner1,
  12. Kim Honselmann1
  1. 1 Department of Surgery, University Medical Center Schleswig Holstein Lübeck Campus, Lubeck, Germany
  2. 2 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  3. 3 Department of Pathology, University Medical Center Freiburg, Freiburg, Germany
  4. 4 Tumorbank Comprehensive Cancer Center Freiburg, Core Facility for Histopathology and Digital Pathology, Medical Center University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg, Germany
  5. 5 Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Steffen Deichmann, Department of Surgery, University Medical Center Schleswig Holstein Lübeck Campus, 23538 Lubeck, Germany; steffen.deichmann{at}uksh.de

Abstract

Aims Due to the known malignant potential and the poor overall prognosis of pancreatic ductal adenocarcinoma (PDAC), the identification of new biomarkers is of utmost importance. It has been reported that integrin alpha 2 (ITGA2), plakophilin 3 (PKP3) and adenylate kinase 4 (AK4) are associated with poor survival and more aggressive malignant behaviour in multiple cancers; however, their role in PDAC is still unknown. Therefore, the aim of this study was to investigate the correlation of ITGA2, PKP3 and AK4 expression with PDAC tumour characteristics and patient survival.

Methods Of 105 patients undergoing oncological pancreatic resection between 2012 and 2018, tissue microarrays were prepared from formalin-fixed, paraffin-embedded PDAC tissues and immunohistochemically stained with PKP3, AK4 and ITGA2. Clinical and pathological patient data were retrieved from the electronic patient charts and correlated with biomarker staining scores.

Results ITGA2 expression was high in 43% of patients with PDAC, whereas AK4 and PKP3 expressions were high in 28% and 57%, respectively. Overall survival was negatively associated with high ITGA2 expression in comparison with low expression (13 months (95% CI 10 to 18 months) vs 25 months (95% CI 20 to 30 months), p<0.001). Expression of AK4 and PKP3 did not correlate with overall survival. Multivariate Cox regression identified ITGA2 as an independent predictor of shorter overall survival in PDAC of different lymph node status and high tumour grade (G3/G4).

Conclusions ITGA2 is an independent prognostic parameter for survival in patients with resected PDAC. PKP3 and AK4 do not appear to have prognostic value for survival in PDAC.

  • pancreatic neoplasms
  • pancreas
  • biomarkers, tumor

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/jclinpath-2022-208176

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    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors All authors contributed to the conception, design, analysis and interpretation of the data. Drafting of the article or critical revision of the article for important intellectual aspects as well as final approval of the version to be published were done by all authors. SD is responsible for the overall content as the guarantor.

    • 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.