Ashida K, Kishimoto Y, Nakamoto K, Wada K, Shiota G, Hirooka Y, Kamisaki Y, Itoh T, Kawasaki H
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
J Cancer Res Clin Oncol. 1997;123(9):489-95. doi: 10.1007/BF01192203.
Carcinogenesis is a multistep process. Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not known well. The present study was conducted to evaluate aberration of the retinoblastoma (RB) gene in HCC and adjacent non-tumorous liver using 22 patients with chronic liver damage accompanying HCC. The specimens obtained by microdissection from paraffin-embedded tissues were analyzed using an assay based on the polymerase chain reaction for highly polymorphic nucleotide sequences of microsatellites in the RB gene. Out of 22 cases, 15 showed constitutional heterozygosity for the microsatellite markers. In 11 (73.3%) of these 15 informative cases, the primary HCC foci showed loss of heterozygosity (LOH). In 8 of these 11 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 20 (64.5%) of 31 microdissected non-tumorous foci. All of the non-tumorous foci showing RB loss were cirrhotic lesions but there were no foci of chronic hepatitis. The remaining 4 cases without LOH in HCC foci showed no LOH in non-tumorous lesions. In our study, LOH of the RB gene was frequently observed in liver cirrhosis surrounding tumor.
致癌作用是一个多步骤过程。大多数肝细胞癌（HCC）之前都有肝硬化，但肝硬化所涉及的基因变化尚不清楚。本研究旨在利用22例伴有HCC的慢性肝损伤患者，评估HCC及癌旁非肿瘤性肝组织中视网膜母细胞瘤（RB）基因的畸变情况。使用基于聚合酶链反应的方法，对从石蜡包埋组织中显微切割获得的标本进行RB基因微卫星高度多态性核苷酸序列分析。在22例病例中，15例显示微卫星标记的构成性杂合性。在这15例信息性病例中的11例（73.3%）中，原发性HCC病灶显示杂合性缺失（LOH）。在这11例双重信息性（原发性HCC中信息性且LOH阳性）病例中的8例中，在31个显微切割的非肿瘤病灶中的20个（64.5%）发现了LOH。所有显示RB缺失的非肿瘤病灶均为肝硬化病变，但无慢性肝炎病灶。其余4例HCC病灶无LOH的病例，其非肿瘤性病变也未显示LOH。在我们的研究中，肿瘤周围的肝硬化组织中经常观察到RB基因的LOH。
