Background: It is believed that in the early stages of hepatocarcinogenesis, some adenomatous hyperplasias (AH) progress to early hepatocellular carcinoma (eHCC), and that many eHCC develop into overt hepatocellular carcinoma (HCC) through nodule-in-nodule formation. However, the proliferative activity of these small nodular lesions has not been fully investigated.
Methods: Cell proliferative activity was assessed by counting nucleolar organizer region-associated proteins (Ag-NOR) in paraffin sections of 12 AH nodules, 25 eHCC nodules, and 8 nodule-in-nodule lesions. In nodule-in-nodule lesions, an area of well-differentiated HCC corresponding to eHCC and a discrete inner nodule area composed of obvious HCC were examined.
Results: Mean Ag-NOR numbers of extranodular parenchyma, AH, and eHCC were 1.35, 1.35, and 1.75 (P < 0.01), respectively. With regard to the relative Ag-NOR number compared with that of parenchyma, there was no overlap between AH and eHCC with a border of 1.1-fold except in one specimen. In nodule-in-nodule lesions, the mean Ag-NOR number (2.53) in the inner nodular area was much higher (P < 0.01) than that of the area of eHCC (mean, 1.88).
Conclusions: A stepwise increment of Ag-NOR number was demonstrated in accordance with the multistep of the AH to eHCC to nodule-in-nodule lesion sequence of hepatocarcinogenesis. Thus, it was proposed that the Ag-NOR count may be a practical and objective parameter for assessing the malignant potential of hepatocellular neoplasms histopathologically.