Nucleolar organizer regions and glycoprotein-hormone alpha-chain reaction as markers of malignancy in endocrine tumours of the pancreas

Histopathology. 1993 Jan;22(1):51-7. doi: 10.1111/j.1365-2559.1993.tb00069.x.


The value of silver staining of nucleolar organizer regions (AgNORs) and human chorionic gonadotropin alpha-chain reaction (HCG-alpha) as markers of malignancy was investigated in 60 primary pancreatic endocrine tumours, 37 of which had metastasized at the time of surgery, and in one of which metastases developed 4 years after surgery. Assessment of AgNORs by digital image analysis revealed few but large AgNORs (mean number 2.5 +/- 1.1; mean area 0.32 +/- 0.1 microns 2) in the 22 benign tumours and many but small AgNORs (mean number 5.1 +/- 1.9, P < 0.05; mean area 0.18 +/- 0.09 microns 2, P < 0.01) in the malignant tumours. Quantification of the number of AgNORs per tumour cell nucleolus (AgNOR distribution score) showed that 96% (26/27) of tumours exhibiting at least 5% of cells with more than six AgNORs per nucleolus showed metastases either at the time of diagnosis or up to 4 years after surgery. HCG-alpha immunoreactive cells were present in 25/38 (66%) malignant tumours and in 4/22 (18%) benign tumours. Combined evaluation of AgNOR distribution and HCG-alpha scores showed a high positive predictive value of 96% in cases with a raised AgNOR distribution score irrespective of the HCG-alpha status. A good negative predictive value (81%) was, however, only obtained if both parameters, AgNOR distribution and HCG-alpha scores, were negative. Thus, investigation of AgNORs and HCG-alpha is helpful in predicting malignancy in a high percentage of pancreatic endocrine tumours.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Endocrine Gland Neoplasms / chemistry
  • Endocrine Gland Neoplasms / pathology*
  • Endocrine Gland Neoplasms / ultrastructure
  • Female
  • Glycoprotein Hormones, alpha Subunit / analysis*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Nucleolus Organizer Region / pathology*
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / ultrastructure
  • Predictive Value of Tests
  • Silver Staining


  • Glycoprotein Hormones, alpha Subunit