Kang Y K, Kim C J, Kim W H, Kim H O, Kang G H, Kim Y I
Department of Pathology, Inje University Seoul Paik Hospital, Seoul, Korea.
Virchows Arch. 1998 Jan;432(1):27-32. doi: 10.1007/s004280050130.
In hepatocarcinogenesis, both de novo and multistep pathways have been suggested and in the latter a dysplastic nodule is the proposed precancerous lesion. In this study, we tried to ascertain whether or not the p53 gene is altered in low-grade/high-grade dysplastic nodules (LDN/HDN) and to determine the role of p53 alteration in multistep hepatocarcinogenesis. Eight hepatocellular carcinomas (HCCs), 9 HDNs, 17 LDNs and 25 cirrhotic nodules (LCs) were examined by polymerase chain reaction-single strand conformation polymorphism/direct sequencing and immunohistochemical staining for p53. Four of the 8 HCCs (50%) revealed p53 overexpression and 2 (25%) had missense mutations. Four of the 9 HDNs (44%) showed weak and/or focal p53 overexpression but none had mutation in the exons examined. Neither p53 overexpression nor mutation was found in 17 LDNs and 25 LCs. These results suggest that p53 mutation might be an unusual event in precancerous lesions of multistep hepatocarcinogenesis (DN-HCC sequence) and may play a less crucial part than in colorectal carcinogenesis.
在肝癌发生过程中，既有从头发生途径，也有多步骤途径，在多步骤途径中，发育异常结节被认为是癌前病变。在本研究中，我们试图确定p53基因在低级别/高级别发育异常结节（LDN/HDN）中是否发生改变，并确定p53改变在多步骤肝癌发生中的作用。通过聚合酶链反应-单链构象多态性/直接测序以及p53免疫组化染色对8例肝细胞癌（HCC）、9例HDN、17例LDN和25例肝硬化结节（LC）进行检测。8例HCC中有4例（50%）显示p53过表达，2例（25%）有错义突变。9例HDN中有4例（44%）显示弱和/或局灶性p53过表达，但在所检测的外显子中均无突变。17例LDN和25例LC中均未发现p53过表达或突变。这些结果表明，p53突变在多步骤肝癌发生（DN-HCC序列）的癌前病变中可能是一个不常见的事件，其作用可能不如在结直肠癌发生中那么关键。
