局灶性结节性增生与肝细胞腺瘤及癌的克隆性和等位基因型分析
Clonality and allelotype analyses of focal nodular hyperplasia compared with hepatocellular adenoma and carcinoma.
作者信息
Cai Yi-Ran, Gong Li, Teng Xiao-Ying, Zhang Hong-Tu, Wang Cheng-Feng, Wei Guo-Lian, Guo Lei, Ding Fang, Liu Zhi-Hua, Pan Qin-Jing, Su Qin
机构信息
Department of Pathology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17, Beijing 100021, China.
出版信息
World J Gastroenterol. 2009 Oct 7;15(37):4695-708. doi: 10.3748/wjg.15.4695.
AIM
To identify clonality and genetic alterations in focal nodular hyperplasia (FNH) and the nodules derived from it.
METHODS
Twelve FNH lesions were examined. Twelve hepatocellular adenomas (HCAs) and 22 hepatocellular carcinomas (HCCs) were used as references. Nodules of different types were identified and isolated from FNH by microdissection. An X-chromosome inactivation assay was employed to describe their clonality status. Loss of heterozygosity (LOH) was detected, using 57 markers, for genetic alterations.
RESULTS
Nodules of altered hepatocytes (NAH), the putative precursors of HCA and HCC, were found in all the FNH lesions. Polyclonality was revealed in 10 FNH lesions from female patients, and LOH was not detected in any of the six FNH lesions examined, the results apparently showing their polyclonal nature. In contrast, monoclonality was demonstrated in all the eight HCAs and in four of the HCCs from females, and allelic imbalances were found in the HCAs (9/9) and HCCs (15/18), with chromosomal arms 11p, 13q and 17p affected in the former, and 6q, 8p, 11p, 16q and 17p affected in the latter lesions in high frequencies (> or = 30%). Monoclonality was revealed in 21 (40%) of the 52 microdissected NAH, but was not found in any of the five ordinary nodules. LOH was found in all of the 13 NAH tested, being highly frequent at six loci on 8p, 11p, 13q and 17p.
CONCLUSION
FNH, as a whole, is polyclonal, but some of the NAH lesions derived from it are already neoplastic and harbor similar allelic imbalances as HCAs.
目的
鉴定局灶性结节性增生（FNH）及其衍生结节的克隆性和基因改变。
方法
检查了12个FNH病变。将12个肝细胞腺瘤（HCA）和22个肝细胞癌（HCC）用作对照。通过显微切割从FNH中识别并分离出不同类型的结节。采用X染色体失活分析来描述其克隆性状态。使用57个标记检测杂合性缺失（LOH）以发现基因改变。
结果
在所有FNH病变中均发现了改变的肝细胞结节（NAH），其被认为是HCA和HCC的前体。在10例女性患者的FNH病变中显示为多克隆性，在所检查的6个FNH病变中均未检测到LOH，结果明显显示出它们的多克隆性质。相比之下，在所有8个HCA和4例女性HCC中显示为单克隆性，并且在HCA（9/9）和HCC（15/18）中发现了等位基因失衡，前者中11p、13q和17p染色体臂受影响，后者病变中6q、8p、11p、16q和17p染色体臂受影响的频率较高（≥30%）。在52个经显微切割的NAH中有21个（40%）显示为单克隆性，但在5个普通结节中均未发现。在所有检测的13个NAH中均发现了LOH，在8p、11p、13q和17p的6个位点上频率很高。
结论
总体而言，FNH是多克隆性的，但从中衍生的一些NAH病变已经是肿瘤性的，并且具有与HCA相似的等位基因失衡。
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