Takagi K, Esumi M, Takano S, Iwai S
First Department of Pathology, Nihon University School of Medicine, Tokyo, Japan.
Liver. 1998 Aug;18(4):272-6. doi: 10.1111/j.1600-0676.1998.tb00165.x.
AIMS/BACKGROUND: Replication errors (RERs) at microsatellite loci are associated with the development of not only hereditary nonpolyposis colon cancer but also sporadic cancers. To examine the association between RERs and human hepatocarcinogenesis, we looked for microsatellite instability in solitary and multiple primary hepatocellular carcinomas (HCCs).
DNAs were extracted from 34 solitary primary HCCs and 14 HCCs with multiple primary cancers. Twelve microsatellite alleles were amplified by PCR from the DNAs, and RERs were assessed by their mobility shift.
RERs were found in only two cases (6%) of solitary HCC and four cases (29%) of HCC with multiple primary cancers. Two of the four HCCs with multiple primary cancers showed RERs at two and three microsatellite loci, respectively. Of 12 microsatellite loci examined, TP53 and D16S476 sensitively detected RERs in HCCs with multiple primary cancers, at a frequency of 23% and 33%, respectively.
RERs are rarely associated with carcinogenesis in human primary HCC, and RER-related genetic alterations may be associated with a part of HCC with multiple primary cancers. If future studies confirm this association, then the two probes TP53 and D16S476 may be useful for the prediction of development of multiple primary cancers with HCC.
目的/背景：微卫星位点的复制错误（RERs）不仅与遗传性非息肉病性结直肠癌的发生有关，还与散发性癌症相关。为了研究RERs与人类肝癌发生之间的关联，我们检测了孤立性和多发性原发性肝细胞癌（HCC）中的微卫星不稳定性。
从34例孤立性原发性HCC和14例伴有多发性原发性癌的HCC中提取DNA。通过PCR从DNA中扩增12个微卫星等位基因，并通过迁移率变化评估RERs。
仅在2例（6%）孤立性HCC和4例（29%）伴有多发性原发性癌的HCC中发现RERs。4例伴有多发性原发性癌的HCC中有2例分别在2个和3个微卫星位点显示RERs。在所检测的12个微卫星位点中，TP53和D16S476能敏感地检测到伴有多发性原发性癌的HCC中的RERs，频率分别为23%和33%。
RERs与人类原发性HCC的致癌作用很少相关，与RER相关的基因改变可能与部分伴有多发性原发性癌的HCC有关。如果未来的研究证实这种关联，那么TP53和D16S476这两种探针可能有助于预测伴有HCC的多发性原发性癌的发生。
