Hsia C C, Nakashima Y, Thorgeirsson S S, Harris C C, Minemura M, Momosaki S, Wang N J, Tabor E
Division of Transfusion Transmitted Diseases, Food and Drug Administration, Bethesda, MD, USA.
Oncol Rep. 2000 Mar-Apr;7(2):353-6.
Mutations of the p53 tumor suppressor gene are common in hepatocellular carcinomas (HCCs). Detection of mutations by sequencing provides more information than immunohistochemical staining, but the equipment needed and the time required make it less practical for use in large-scale studies or in studies in developing countries. The degree of correlation between results obtained with these two methods has been studied in various tumors but has not been well-established in human HCCs. Paraffin sections of HCCs of 28 patients from Qidong, China were immunohistochemically stained using monoclonal antibody to p53. In addition, exons 5-8 of the p53 gene were sequenced in these HCCs. Of the 28 HCCs, nine had 0-9% of nuclei stained for p53, and 19 had 50-95% stained. Mutations in p53 exons 5-8 were found in 17/28 (61%) HCCs, including 15 at codon 249 (exon 7), one at codon 198 (exon 6), and one at codon 175 (exon 5). Among these 17 cases with p53 mutations, 16 cases (94%) had 50-95% of nuclei stained. Among 11 HCCs with no mutations by sequencing, 8 were also negative by immunohistochemistry (0-9% of nuclei stained) (73%) (the five HCCs with no staining whatsoever all had wild-type p53). Immunohistochemical staining to detect p53 mutations in human HCCs detected most mutations that were detected by sequencing (94% sensitivity, 73% specificity), and this method is therefore suitable when sequencing cannot be performed.
p53肿瘤抑制基因的突变在肝细胞癌（HCC）中很常见。通过测序检测突变比免疫组织化学染色提供的信息更多，但所需设备和时间使其在大规模研究或发展中国家的研究中不太实用。这两种方法所得结果之间的相关程度已在各种肿瘤中进行了研究，但在人类HCC中尚未得到充分证实。对来自中国启东的28例HCC患者的石蜡切片用p53单克隆抗体进行免疫组织化学染色。此外，对这些HCC中的p53基因外显子5 - 8进行测序。在28例HCC中，9例p53染色的细胞核比例为0 - 9%，19例为50 - 95%。在28例HCC中有17例（61%）在p53外显子5 - 8中发现突变，包括15例在密码子249（外显子7）、1例在密码子198（外显子6）和1例在密码子175（外显子5）。在这17例有p53突变的病例中，16例（94%）的细胞核染色比例为50 - 95%。在11例测序未发现突变的HCC中，8例免疫组织化学也为阴性（细胞核染色比例为0 - 9%）（73%）（5例完全无染色的HCC均具有野生型p53）。免疫组织化学染色检测人类HCC中的p53突变能检测到大多数通过测序发现的突变（敏感性为94%，特异性为73%），因此当无法进行测序时，该方法是适用的。
