Clonal analysis of macronodules in cirrhosis
Clonal analysis of macronodules in cirrhosis
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DOI：
10.1002/hep.510280409
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发表时间：
1998-10-01
期刊：
影响因子：
13.5
通讯作者：
Bedossa, P
中科院分区：
文献类型：
--
作者：
Paradis, V;Laurendeau, I;Bedossa, P
几种观点认为，大多数发生在人的肝硬变中的肝细胞癌是由大的肝细胞结节或大结节引起的。除了具有明显肝细胞癌特征的结节外，尚无统一的标准能够区分良性再生和肿瘤性、潜在恶性的大结节，需要能够准确区分那些将演变为肝细胞癌的病变的替代标记物。在这项研究中，我们通过分析X染色体失活来研究从8例女性移植的肝硬变中分离出的26个大结节的克隆性，这表明人类雄激素受体基因(HUMARA)的甲基化状态。对于每个大结节，评估了一大组病理特征，并将其分为四组：完全良性结节(类型1)、低度发育不良结节(类型2)、高度发育不良结节(类型3)和肝细胞癌(类型4)。克隆分析表明，14个大结节(54%)为单克隆性，12个(46%)为多克隆。11个结节中的5个(45%)来自完全良性和低度发育不良结节(类型1和2)，9个(60%)来自高度发育不良结节和肝细胞癌(类型3和4型)。无论是肝硬变的病因，还是大结节的大小或组织学分类都与克隆状态无关。结论：对大结节的克隆性分析可以区分单克隆性大结节和多克隆性大结节，因为单克隆性大结节容易演变为肝癌，因此确定大结节的克隆性状态可以为评估这些病变的预后提供额外的信息。
Several arguments suggest that most hepatocellular carcinomas (HCCs) occurring in human cirrhotic livers arise from large hepatocellular nodules or macronodules. Except for nodules with obvious features of HCC, there exist no consistent criteria enabling the differentiation between benign regenerative and neoplastic, potentially malignant macronodules, Surrogate markers able to accurately discriminate those lesions that will evolve toward a HCC are required. In this study, we investigated the clonality of 26 macronodules isolated from eight cases of explanted cirrhotic livers in women by analyzing X-chromosome inactivation, as indicated by the methylation status of the human androgen receptor gene (HUMARA). For each macronodule, a large set of pathological features was evaluated and used to classify the macronodules into four groups: entirely benign-looking nodule (type 1), low-grade dysplastic nodule (type 2), high-grade dysplastic nodule (type 3), and HCC (type 4). Clonal analysis showed that 14 macronodules (54%) were monoclonal and 12 (46%) were polyclonal. Monoclonality was detected in 5 of 11 (45%) nodules from groups of entirely benign-looking and low-grade dysplastic nodules (types 1 and 2) and in 9 of 14 (60%) nodules from the group of high-grade dysplastic nodule and HCC (types 3 and 4). Neither the etiology of cirrhosis nor the size or histological classification of macronodules was correlated with the clonal status, In conclusion, clonal analysis of macronodules enables the differentiation between mono- and polyclonal macronodules in cirrhosis, Because monoclonal macronodules are prone to evolve to HCC, the determination of the clonal status of a macronodule could provide additional information for evaluating the prognosis of these lesions.