Terris B, Ingster O, Rubbia L, Dubois S, Belghiti J, Feldmann G, Degott C, Hénin D
Service d'Anatomie Pathologique, Hôpital Beaujon, Clichy, France.
J Hepatol. 1997 Aug;27(2):313-9. doi: 10.1016/s0168-8278(97)80177-8.
BACKGROUND/AIMS: Little is known about genetic alterations in large or small liver cell dysplasia. The aim of this study was to determine whether these lesions present numerical chromosome aberrations.
Eight patients with hepatocellular carcinoma on cirrhosis, five with large liver cell dysplasia and three with small liver cell dysplasia, were analysed by in situ hybridization with different centromeric nucleic acid probes specific respectively for chromosomes 1, 7, 17 and 18. In each case results were compared between dysplastic, tumoral and non-dysplastic cirrhotic cells. Four normal livers were also studied with the same method and served as cytogenetic controls.
All cases of large liver cell dysplasia dysplayed a polysomic population for each investigated chromosome. A high variability of numerical chromosome aberrations was observed with a copy number of chromosomes which ranged from two to more than six. By contrast, only one case of small liver cell dysplasia showed chromosomal anomalies. Numerical aberrations of at least one chromosome were observed in six of the eight hepatocellular carcinoma while the non-dysplastic cirrhosis and normal liver always showed a diploid pattern.
These results demonstrate that cellular modifications in large liver cell dysplasia coexist with an early acquisition of genomic alterations, supporting the view that these phenotypic changes are preneoplastic.
背景/目的：关于大或小肝细胞发育异常中的基因改变知之甚少。本研究的目的是确定这些病变是否存在染色体数目异常。
对8例肝硬化合并肝细胞癌患者、5例大肝细胞发育异常患者和3例小肝细胞发育异常患者，分别用针对1、7、17和18号染色体的不同着丝粒核酸探针进行原位杂交分析。在每种情况下，对发育异常细胞、肿瘤细胞和非发育异常的肝硬化细胞的结果进行比较。还用相同方法研究了4个正常肝脏，并作为细胞遗传学对照。
所有大肝细胞发育异常病例的每个研究染色体均显示多倍体群体。观察到染色体数目异常的高度变异性，染色体拷贝数范围从2到6个以上。相比之下，只有1例小肝细胞发育异常显示染色体异常。8例肝细胞癌中有6例观察到至少1条染色体的数目异常，而非发育异常的肝硬化和正常肝脏总是显示二倍体模式。
这些结果表明，大肝细胞发育异常中的细胞改变与基因组改变的早期获得共存，支持这些表型变化是肿瘤前病变的观点。
