Genomic Microsatellite Alterations And Clinicopathological Significance In Chinese Hepatocellular Adenomas

Objective: The Clinicopathological Characteristics of166Chinese hepatocellularadenoma (HCA) are observed,Some of which microsatellite alterations are analyzed inorder to we further understand their pathogenesis and significance in molecular pathologyDiagnosis.Methods: The clinicopathological parameters of166patients with HCA wereanalyzed by statistical analysis systematically,60cases of whose tissues were harvestedby microdissection,12Microsatellite markers of HCA patients whose Microsatelliteinstability (MSI) and loss of heterozygosity(LOH) were checked by PCR-SSCPmethods, the correlation between clinicopathological characteristics and microsatellitealterations was compared and analysed.Results: Of166HCA,114cases (68.44%) were men and52cases (31.56%)were women，with average age40.0±2.1and33.4±3.8respectively，while constituentratio of gender was significantly different among10-30and30-50and50-in ages(P＜0.05). Of154HCA, Body Mass Index (BMI) of male and female were significantlydifferent among＜24and24-28and≥28(kg/㎡)in BMI(P＜0.05). Of166HCA,constituent ratio of female in those tumors bigger than10㎝in sizes were significantlythose ｏf male (P＜0.05). immunohistochemistry：The expression of glypican-3inHCA was lower than in well differentiated hepatocellular carcinomas; β-catenin in HCAwas far higher than that in the focal nodular hyperplasia (FNH). Concordance betweenmismatch repair gene (MNR) Panel (five kinds of international standards ofmicrosatellite) and twelve microsatellite markers was77.5%,which of the twoinspection means was a high degree of consistency(P＞0.05). Of12microsatellitemarkers, overall incidence rates of MSI and LOH were35.72%and8.82%respectively.Of MNR Panel in40HCA, MSI-H in drinking group was significantly higher than in those non-drinking group (P＜0.05). Of12microsatellite markers, the frequencies ofMSI were significantly different among sex（D11S4207）and clinical history of EssentialHypertension(EHT) of HCA（D2S2726）(P＜0.05). The frequencies of LOH onD6S1581in women were significantly higher than in men (P＜0.05).The occurance of MSI–H in40cases was significantly associated with drinking inmale (P＜0.05). MSI in the female were significantly more frequent in patients withbigger than24in BMI (P＜0.05).Conclusion:（1）Chinese HCA is frequently in middle-aged men,it is differentfrom western country in young women,which suggest the mechanism and pathogeny ofChinese HCA are different from foreigners. Analysis of microsatellite alterationssuggest pathogenesis of Chinese HCA are associated with metabolic disturbances ofvarious relevant:1.MSI of female HCA are associated with D11S4207,which may occur throughconstant and specific mechanism in NF-κB pathway.2.MSI of HCA of clinical history of Essential Hypertension are associated withD2S2726, which may occur through a constant and specific mechanism in the HNF1αinactivated pathway.3.MSI of female HCA in≥24in BMI are associated with D6S2075and LOH offemale HCA are associated with D6S1581,which may occur through constant andspecific mechanism in ERK and AKT pathway.（2）The use of MNR Panel testing seemsto be a robust standards approach。MSI，which represents mismatch repair gene pathway，play a more important role inmolecular variation of HCA; LOH，which represents tumor sppressor gene pathwayarranges as the part of Mechanism.It will be propitious to Molecular Genotype andprovide a kind of important theory basis which contributed to assess mechanism of HCAand the correlation of histopathology alterations.