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

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Abstract
The value of silver staining of nucleolar organizer regions (AgNORs) and human chorionic gonadotropin α-chain reaction (HCG-α) 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 ± in the 22 benign tumours and many but small AgNORs (mean number 5.1 ± 1.9, P2. P<0.01) in the malignant tumours. Quantification of the number of AgNORs per tumour cell AgNOR distribution score) showed that 96% (26/27) of tumours exhibiting at least 5% of cells with more six AgNORs per nucleolus showed metastases either at the time of diagnosis or up to 4 years after surgery. HCG-α immunoreactive cells were present in 25/38 (66%) malignant tumours and in 4/22 (18%) benign tumours. Combined evaluation of AgNOR distribution and HCG-α scores showed a high positive predictive value of 96% in cases with a raised AgNOR distribution score irrespective of the HCG-α status. A good negative predictive value (81%) was, however, only obtained if both parameters, AgNOR distribution and HCG-α scores, were negative. Thus, investigation of AgNORs HCG-α is helpful in predicting malignancy in a high percentage of pancreatic endocrine tumours.