Purpose: Hepatocellular cardnoma (HCC) shows various molecular and genetic alterationsin its development and progression. Recently, microsatellite instability (MSI) and the loss ofheterozygosity (LOH), have been postulated as useful prognostic factors in many malignanttumors. LOH is related to the allelic loss of various tumor suppressor genes, however, MSIhas been found to be the result of a mismatched DNA pairing. Our objectives were toevaluate MSI and p53 gene LOH and to correlate this to clinicopathological factors.
Methods: MSI analysis was performed by using polymerase chain reaction with 5microsatellite markers (BAT25, BAT26, D2S123, D5S346 and D17S250 recommended in the1998 NCI International WorkshoP) on 50 surgically resected tumors. p53 LOH was detectedwith 4 markers (D17S796, TP53, D17S5, D17S513).
Results: MSI and p53 LOH were detected in 30% and 66%, respectively. 18% of HCCsexhibited MSI in 5 NCI-recommended markers and 18% of HCCs demonstrated MSI in 4 p53markers. MSI was mostly detected in BAT25 and BAT26 markers. MSI was more frequentlydetected in tumor grade I, small HCC, and non-lymphovascular group. For the most part, P53LOH was detected by D17S513 marker (38.1%). p53 LOH results were correlated with highertumor grade and invasiveness. LOH-High group showed a significant correlation withadvanced HCCs and lymphovascular invasion. There was no demonstrated correlationbetween MSI and p53 LOH was not demonstrated.
Conclusion: These results suggest that MSI may be involved to some extent inhepatocarcinogenesis and tumor invasion. Also MSI and p53 gene LOH may be a usefulclinical indicator in determining the prognosis among patients with HCC.
|