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Exploring the Dynamic Interaction Between Pituitary Neuroendocrine Tumors (Pit-NETs) Cells and Their Angiogenic

Mihaela Cozma1,2, Anca Maria Cimpean3,4,5,6, Mihail Parnov1,2

  • 1Department of Pathology, Nicolae Testemitanu State University of Medicine and Pharmacy, MD 2004 Chisinau, Moldova.

Current Issues in Molecular Biology
|January 30, 2026
PubMed
Summary

Simultaneous proliferation of pituitary tumors (PitNETs) and endothelial cells correlates with VEGF expression. Digital analysis of MIB1 and VEGF aids in risk stratification for specific PitNET subtypes.

Keywords:
PitNETsQuPathdigital image analysisendothelial cellsproliferationtumor cells

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Area of Science:

  • Endocrinology
  • Pathology
  • Digital Pathology

Background:

  • Simultaneous proliferation of pituitary neuroendocrine tumors (PitNETs) and endothelial cells is a debated topic in pituitary pathology.
  • Previous research has not compared the MIB1 Labeling Index (MIB1 LI) in PitNETs and their stromal endothelial compartments concerning VEGF expression.

Purpose of the Study:

  • To investigate the relationship between MIB1 LI in PitNETs and stromal endothelial cells.
  • To assess the connection between dual proliferation and VEGF protein and gene expression.
  • To determine if dual proliferation characterizes specific PitNET subtypes using digital image analysis (DIA).

Main Methods:

  • Analyzed 109 PitNETs using immunohistochemistry for CD34 (endothelial cells) and MIB1 (proliferation).
  • Assessed VEGF expression via immunohistochemistry and RNA scopes.
  • Employed QuPath-based DIA to quantify MIB1 nuclear expression in tumor and endothelial cells.

Main Results:

  • MIB1 LI demonstrated a correlation with VEGF mRNA and protein levels.
  • Prolactin-secreting and non-functioning PitNETs exhibited high MIB1 LI in stromal endothelial cells.
  • A significant correlation (p=0.01) was found between MIB1 LI in tumor cells and endothelial cells.
  • VEGF and hormone profiles influenced MIB1 LI in tumor and endothelial cells differently.
  • Tumor-endothelial cell proliferative interactions were specific to prolactin-secreting and non-functioning PitNETs.

Conclusions:

  • Digital analysis of MIB1 and VEGF expression offers a potential method for PitNET risk stratification.
  • Tumor-endothelial cell proliferation is a characteristic feature of specific PitNET subtypes, namely PRL-secreting and non-functioning adenomas.
  • The study highlights the utility of DIA in assessing complex cellular interactions in pituitary pathology.