Selected markers of proliferation and apoptosis in the parathyroid lesions: a spatial visualization and quantification

J Mol Histol. 2008 Oct;39(5):509-17. doi: 10.1007/s10735-008-9190-1. Epub 2008 Aug 24.


The aim of the paper was to apply a method for quantitative assessment of proliferation and apoptosis markers, based on their 3D visualization, in cases of parathyroid adenoma and hyperplasia. Material was obtained from 49 patients (32 females and 17 males) with primary hyperparahyroidism. Quantitative immunohistochemistry studies of Ki-67, proliferating cell nuclear antigen (PCNA) and bcl-2 were performed on digital microscopy images with the use of 3D visualization. The use of spatial visualization method allowed us to perform objective quantitative assessment of the studied immunohistochemical markers. The average cell nuclear fraction of Ki67+ was 1.8% in hyperplasia and 1.9% in adenoma cases while 3.5% in the controls. The highest expression of PCNA was found in parathyroid hyperplasia (22.9%) and significantly decreased in adenoma (12.5%) and in the control group (16.8%). The lower expression of bcl-2 in hyperplasia cases (mean area fraction of 0.172 per 1 mum(2), in contrast to 0.643 in adenomas and 0.648 in control) suggested that principal cells can be ready for apoptosis and may confirm the important role of bcl-2 protein in etiopathogenesis of hyperplasia of the parathyroid gland while PCNA might be a useful marker for differentiating adenoma from early hyperplasia in primary hyperparahyroidism cases.

MeSH terms

  • Adult
  • Apoptosis*
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperparathyroidism / metabolism*
  • Hyperparathyroidism / pathology*
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Image Processing, Computer-Assisted*
  • Immunohistochemistry / methods
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Parathyroid Glands / metabolism*
  • Parathyroid Glands / pathology*
  • Parathyroid Neoplasms / metabolism*
  • Parathyroid Neoplasms / pathology*
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2