Nucleolar organizer regions and glycoprotein-hormone alpha-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.
Rüschoff
J
J
Department of Pathology, University of Regensburg, Germany.
Willemer
S
S
Brunzel
M
M
Trautmann
M E
ME
Frank
M
M
Arnold
R
R
Klöppel
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D004701:Endocrine Gland Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000032:analysis*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009697:Nucleolus Organizer Region / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D011237:Predictive Value of Tests; D016622:Silver Staining
D015292:Glycoprotein Hormones, alpha Subunit