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

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.