Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China.
OBJECTIVE
To determine the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC).


METHODS
Loss of heterozygosity (LOH) and microsatellite instability (MSI) of 55 microsatellite loci were detected with PCR-based microsatellite polymorphism analyses in tumors and corresponding noncancerous liver tissues of 56 surgically resected HCCs using the MegaBACE 500 automatic DNA analysis system.


RESULTS
LOH was found in 44 of 56 HCCs (78.6%) at one or several loci. Frequencies of LOH on 1p, 4q, 8p, 16q, and 17p were 69.6% (39/56), 71.4% (40/56), 66.1% (37/56), 66.1% (37/56), and 64.3% (36/56), respectively. MSI was found in 18 of 56 HCCs (32.1%) at one or several loci. Ten of fifty-six (17.9%) HCCs had MSI-H. Serum HBV infection, alpha-fetoprotein concentration, tumor size, cirrhosis, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with LOH on certain chromosome regions.


CONCLUSIONS
Frequent microsatellite alterations exist in HCC. LOH, which represents a tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis. MSI, which represents a mismatch repair gene pathway, is a rare event during liver carcinogenesis. Furthermore, LOH on certain chromosome regions may be correlated with clinicopathological characteristics in HCC.
Zhang
Shu-Hui
SH
Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. zhangshuhui100@sohu.com
Cong
Wen-Ming
WM
Xian
Zhi-Hong
ZH
Wu
Meng-Chao
MC
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002681:China; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged