Aoki K, Sakamoto M, Hirohashi S
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer. 1994 Jan 15;73(2):289-93. doi: 10.1002/1097-0142(19940115)73:2<289::aid-cncr2820730209>3.0.co;2-g.
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.
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.
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).
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.
人们认为在肝癌发生的早期阶段，一些腺瘤样增生（AH）会进展为早期肝细胞癌（eHCC），并且许多eHCC会通过结节中结节的形成发展为显性肝细胞癌（HCC）。然而，这些小结节性病变的增殖活性尚未得到充分研究。
通过对12个AH结节、25个eHCC结节和8个结节中结节病变的石蜡切片中核仁组织区相关蛋白（Ag-NOR）进行计数来评估细胞增殖活性。在结节中结节病变中，检查对应于eHCC的高分化HCC区域和由明显HCC组成的离散内部结节区域。
肝外实质、AH和eHCC的平均Ag-NOR数分别为1.35、1.35和1.75（P < 0.01）。关于与实质相比的相对Ag-NOR数，除一个标本外，AH和eHCC之间没有重叠，边界为1.1倍。在结节中结节病变中，内部结节区域的平均Ag-NOR数（2.53）比eHCC区域的平均Ag-NOR数（1.88）高得多（P < 0.01）。
根据肝癌发生的AH到eHCC再到结节中结节病变序列的多步骤过程，证实了Ag-NOR数的逐步增加。因此，有人提出Ag-NOR计数可能是一种在组织病理学上评估肝细胞肿瘤恶性潜能的实用且客观的参数。
