Clonality and allelotype analyses of focal nodular hyperplasia compared with hepatocellular adenoma and carcinoma.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Pathology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17, Beijing 100021, China.
Yi-Ran
YR
Cai
Li
L
Gong
Xiao-Ying
XY
Teng
Hong-Tu
HT
Zhang
Cheng-Feng
CF
Wang
Guo-Lian
GL
Wei
Lei
L
Guo
Fang
F
Ding
Zhi-Hua
ZH
Liu
Qin-Jing
QJ
Pan
Qin
Q
Su
D018248:Adenoma, Liver Cell / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D049951:X Chromosome Inactivation; D055815:Young Adult