Epithelial-Immune Cell Crosstalk in Salivary Gland Tumors: Implications for Tumor Progression and Diagnostic Assessment

  • Martina Sausa
  • , Giuseppe Vergilio
  • , Rosario Barone
  • , Rossana Porcasi
  • , Prince Ofori
  • , Fatima Azhraa Haddad
  • , Francesca Rappa*
  • , Francesca Levi-Schaffer
  • , Angelo Leone*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

This study explores immunophenotypic and angiogenic profiles in salivary gland tumors (SGTs), focusing on epithelial–mesenchymal dynamics and immune–stromal interactions. Immunohistochemical analysis of E-cadherin, Vimentin, mast cell tryptase (MCT), CD300a, CK18, CD31, and vascular endothelial growth factor (VEGF) was performed in normal salivary tissue, pleomorphic adenomas (PA), and squamous cell carcinomas (SCCs) to assess epithelial plasticity, mast cell (MC) involvement, and vascular remodeling. Normal glands showed compartmentalized E-cadherin (epithelial) and Vimentin (mesenchymal) expression, with stromal MCs positive for MCT and CD300a. PA exhibited reduced E-cadherin, increased Vimentin, and atypical co-localization of CK18 with MCT/CD300a in ductal cells, indicating immune–epithelial plasticity. SCC displayed epithelial–mesenchymal transition (EMT), architectural disruption, and reduced MCT/CD300a. Notably, diminished MCT may reflect either decreased MCs density or prior degranulation, with possible diffuse MCT in stroma. Angiogenic profiling showed maximal CD31 in PA and minimal in SCC, while VEGF peaked in normal tissue, suggesting deregulated angiogenesis. SGT progression involves immune–epithelial plasticity, vascular deregulation, and stromal reprogramming. Immune marker localization within epithelial cells challenges histogenetic models and may inform prognostic assessment and targeted therapeutic strategies.

Original languageEnglish
Article number10199
JournalInternational Journal of Molecular Sciences
Volume26
Issue number20
DOIs
StatePublished - Oct 2025

Bibliographical note

Publisher Copyright:
© 2025 by the authors.

Keywords

  • CD300a
  • mast cell tryptase
  • mast cells
  • pleomorphic adenoma
  • salivary glands
  • squamous cells carcinoma

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