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

J Clin Pathol. 2023 Aug;76(8):541-547. doi: 10.1136/jclinpath-2022-208176. Epub 2022 Apr 8.

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.

Keywords: biomarkers, tumor; pancreas; pancreatic neoplasms.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal* / surgery
  • Humans
  • Integrin alpha2
  • Pancreatic Neoplasms* / pathology
  • Pancreatic Neoplasms* / surgery
  • Prognosis

Substances

  • Integrin alpha2
  • Biomarkers, Tumor