Aryl hydrocarbon receptor interacting protein (AIP) significantly influences prognosis of pancreatic carcinoma

Ann Diagn Pathol. 2021 Aug:53:151742. doi: 10.1016/j.anndiagpath.2021.151742. Epub 2021 Mar 31.

Abstract

Introduction: Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. Aryl hydrocarbon receptor interacting protein (AIP) in one of AHR ligands. The aim of this study is to analyze the prognostic influence of AIP in pancreatic carcinoma.

Material and methods: Retrospective case series with immunohistochemical analysis of AIP. We have estimated a multivariate Cox's model for the outcome (progression free and overall survival).

Results: 204 patients were included in the study. As expected prognosis was poor and 67.8% died of disease. As for AIP 9.8% of the cases showed nuclear staining of the epithelial tumor cells and 59.4% a cytoplasmic one. Stroma was stained in 53.1% of the cases. Univariate survival analysis revealed a significantly worse prognosis of patients with cytoplasmic AIP expression (stroma and epithelium), but nuclear expression was associated to a better prognosis. In the multivariate analysis stromal AIP expression was an independent prognosticator of progression free survival, together with pT stage, histological grade and history of diabetes.

Discussion: AIP Is a conserved cochaperone protein binding to many proteins. AIP has been proposed as a potential tumor suppressor gene. To date, no study has analyzed the immunohistochemical expression of AIP in pancreatic carcinoma. Our results indicate that both epithelial and stromal cytoplasmic expression of AIP is associated to bad prognosis, while nuclear translocation seems to improve prognosis.

Conclusion: Although we must deepen into the complex signaling pathways underlying this potential association, our results open a way to inhibiting AHR as a potential target against pancreatic carcinoma.

Keywords: Aryl hydrocarbon receptor; Aryl hydrocarbon receptor interacting protein; Pancreatic carcinoma; Prognosis.

MeSH terms

  • Aged
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MAP Kinase Signaling System / genetics
  • Male
  • Margins of Excision
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Staging / methods
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Progression-Free Survival
  • Receptors, Aryl Hydrocarbon / drug effects
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Retrospective Studies
  • Survival Analysis

Substances

  • Intracellular Signaling Peptides and Proteins
  • Receptors, Aryl Hydrocarbon
  • aryl hydrocarbon receptor-interacting protein