Paradis V, Laurendeau I, Vidaud M, Bedossa P
Service d'Anatomie Pathologique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France.
Hepatology. 1998 Oct;28(4):953-8. doi: 10.1002/hep.510280409.
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 15 (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.
有几个论据表明，人类肝硬化肝脏中出现的大多数肝细胞癌（HCC）起源于大肝细胞结节或大结节。除了具有明显HCC特征的结节外，目前尚无一致的标准能够区分良性再生性和肿瘤性、潜在恶性的大结节。需要能够准确区分那些将演变为HCC的病变的替代标志物。在本研究中，我们通过分析X染色体失活情况（由人类雄激素受体基因（HUMARA）的甲基化状态指示），研究了从8例女性移植肝硬化肝脏中分离出的26个大结节的克隆性。对于每个大结节，评估了大量病理特征，并将大结节分为四组：完全良性外观结节（1型）、低级别发育异常结节（2型）、高级别发育异常结节（3型）和HCC（4型）。克隆分析显示，14个大结节（54%）为单克隆，12个（46%）为多克隆。在完全良性外观和低级别发育异常结节组（1型和2型）的11个结节中有5个（占45%）检测到单克隆性，在高级别发育异常结节和HCC组（3型和4型）的15个结节中有9个（占60%）检测到单克隆性。肝硬化的病因、大结节的大小或组织学分类均与克隆状态无关。总之，大结节的克隆分析能够区分肝硬化中的单克隆和多克隆大结节。由于单克隆大结节易于演变为HCC，确定大结节的克隆状态可为评估这些病变的预后提供额外信息。
