[Study on loss of heterozygosity and microsatellite instability in hepatocellular carcinoma].
OBJECTIVE
To investigate the role of loss of heterozygosity (LOH) in tumor suppressor genes (TSG) and microsatellite instability (MSI) in hepatocarcinogenesis, as well as their correlation with clinicopathologic features.


METHODS
LOH in 6 TSG (APC, DCC, MCC, OGG1, p53 and RB1) was detected in 36 informative cases of hepatocellular carcinoma (HCC), among 92 surgically resected HCC. Thirteen polymorphic microsatellite markers were also studied in 15 of these cases by microdissection-based PCR amplification and direct DNA sequencing. The correlation between genetic alterations and clinicopathologic features was analyzed.


RESULTS
The overall incidence of LOH in HCC was 41.7% (15/36). There was no LOH in MCC gene. 46.2% (6/13) microsatellites showed LOH in 9 of the 15 cases of HCC (60%). Certain clinicopathologic differences were observed between cases (number = 7) with LOH in APC, OGG1 and DCC ("type I") and cases (number = 8) with LOH in p53 and RB1 ("type II"). The mean tumor size of these two types was 2.9 (+/- 1.7) cm and 7.2 (+/- 3.4) cm, respectively (P < 0.01); and the mean survival was 72.0 (+/- 38.6) months, and 51.0 (+/- 30.4) months, respectively (P < 0.05).


CONCLUSIONS
Compared with MSI pathway, LOH pathway plays a more important role in the development of HCC. A multistep hepatocarcinogenesis is likely, with LOH in APC, OGG1 and DCC ("type I") being an early event and LOH in p53 and RB1 ("type II") being a late event. On the other hand, MCC gene seems to play no role in the whole process.
Cong
Wen-Ming
WM
Department of Pathology, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China. wmcong@smmu.edu.cn
Zhang
Shu-Hui
SH
Xian
Zhi-Hong
ZH
Wu
Wei-Qing
WQ
Wu
Meng-Chao
MC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D017491:Genes, APC; D016163:Genes, DCC; D017431:Genes, MCC; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged