Determination of the molecular relationship between multiple tumour nodules in hepatocellular carcinoma differentiates multicentric origin from intrahepatic metastasis

Determination of the molecular relationship between multiple tumour nodules in hepatocellular carcinoma differentiates multicentric origin from intrahepatic metastasis
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DOI:
10.1002/path.1287
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发表时间:
2003-03-01
影响因子:
7.3
通讯作者:
Lee, JMF
Lee, JMF
中科院分区:
医学1区
文献类型:
--
作者:
Ng, IOL;Guan, XY;Lee, JMF

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本研究的目的是确定个体患者中肝细胞癌(HCC)多个肿瘤结节之间的分子关系,并评估其克隆性,这可能具有预后意义。在11例多发性HCC患者的25个HCC结节中,使用DNA指纹杂合性缺失(洛)分析、比较基因组杂交(CGH)和B型肝炎病毒(HBV)整合模式来确定单个患者内结节的克隆关系。洛缺失和CGH结果显示,11例患者中有4例(36%)的多原发性肝癌具有不同的克隆性,属于多中心起源,而其余7例(64%)的多原发性肝癌具有相似的克隆性关系,属于肝内转移。在选定的病例中,HBV整合模式有助于确认克隆性结果。大体外观,大小,位置和组织学的肿瘤不能准确预测其克隆起源在每一个案件。DNA改变的评估可以精确确定一名患者中多个HCC的克隆性。在这些分子学方法中,洛分析可用于评估大多数患者甚至在手术切除前的肿瘤克隆性,因为该测定可容易地常规应用于肝活检或细针抽吸。版权所有(C)2003约翰威利父子有限公司。
The purpose of this study was to determine the molecular relationship between multiple tumour nodules in hepatocellular carcinoma (HCC) within individual patients and to evaluate their clonality, which may bear prognostic significance. In 25 HCC nodules from 11 patients with multiple HCCs, the clonal relationships of the nodules within individual patients were determined using DNA fingerprinting with loss of heterozygosity (LOH) assay, comparative genomic hybridization (CGH), and hepatitis B virus (HBV) integration pattern. Both LOH assay and CGH indicated that in four (36%) of the 11 patients; the multiple HCCs had different clonalities and hence were of multicentric origin, whereas in the remaining seven (64%) patients, the multiple HCCs had similar clonal relationships and were intrahepatic metastases. In selected cases, the HBV integration pattern helped to confirm the clonality results. Gross appearance, size, location, and histology of the tumours could not accurately predict their clonal origin in every case. Assessment of DNA alterations allows precise determination of the clonality of multiple HCCs within one patient. Of these molecular methods, LOH analysis can be used to evaluate tumour clonality in most patients even before surgical resection, since this assay can be readily applied routinely to either liver biopsies or fine needle aspirates. Copyright (C) 2003 John Wiley Sons, Ltd.