Korean J Hepatobiliary Pancreat Surg.  2009 Sep;13(3):143-151.

Microsatellite Instability and p53 Gene Loss of Heterozygosity in Hepatocellular Carcinoma

• Kim JS
• Lim MS
• Kim DJ
• Kim JS
• Kim KS
• Kim HK
• Cho SJ
• Kwon MJ
• Nam ES
• Choi KC
• Shin HS
• Chae GB

Abstract

PURPOSE
Hepatocellular carcinoma (HCC) shows various molecular and genetic alterations in its development and progression. Recently, microsatellite instability (MSI) and the loss of heterozygosity (LOH), have been postulated as useful prognostic factors in many malignant tumors. LOH is related to the allelic loss of various tumor suppressor genes, however, MSI has been found to be the result of a mismatched DNA pairing. Our objectives were to evaluate MSI and p53 gene LOH and to correlate this to clinicopathological factors.
METHODS
MSI analysis was performed by using polymerase chain reaction with 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346 and D17S250 recommended in the 1998 NCI International Workshop) on 50 surgically resected tumors. p53 LOH was detected with 4 markers (D17S796, TP53, D17S5, D17S513).
RESULTS
MSI and p53 LOH were detected in 30% and 66%, respectively. 18% of HCCs exhibited MSI in 5 NCI-recommended markers and 18% of HCCs demonstrated MSI in 4 p53 markers. MSI was mostly detected in BAT25 and BAT26 markers. MSI was more frequently detected in tumor grade I, small HCC, and non-lymphovascular group. For the most part, p53 LOH was detected by D17S513 marker (38.1%). p53 LOH results were correlated with higher tumor grade and invasiveness. LOH-High group showed a significant correlation with advanced HCCs and lymphovascular invasion. There was no demonstrated correlation between MSI and p53 LOH was not demonstrated.
CONCLUSION
These results suggest that MSI may be involved to some extent in hepatocarcinogenesis and tumor invasion. Also MSI and p53 gene LOH may be a useful clinical indicator in determining the prognosis among patients with HCC.

Keyword

Carcinoma; Hepatocellular; Chromosomes; Human; 17; Microsatellite Instability; Loss of Heterozygosity; p53 gene

MeSH Terms

Carcinoma, Hepatocellular
DNA
Genes, p53
Genes, Tumor Suppressor
Humans
Loss of Heterozygosity
Microsatellite Instability
Microsatellite Repeats
Polymerase Chain Reaction
Prognosis
Succinimides
DNA
Succinimides