Differential expression of cell cycle regulators in HCV-infection and related hepatocellular carcinoma

• Published in: World journal of hepatology Vol. 2; no. 1; pp. 32 - 41
• Main Authors: Bassiouny, Azza E El, Nosseir, Mona M, Zoheiry, Mona K, Ameen, Noha A, Abdel-Hadi, Ahmed M, Ibrahim, Ibrahim M, Zada, Suher, El-Deen, Abdel-Hakeem Saad, El-Bassiouni, Nora E
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 27.01.2010
• Subjects: carcinoma; Cell; Chronic; cirrhosis; cycle; Cyclin; hepatitis; Hepatocellular; Liver; Original; p21; p27; Rb/p105; Chronic hepatitis C; p27; Rb/p105; Cell cycle; Hepatocellular carcinoma; Cyclin E; Cyclin D1; Liver cirrhosis; p21
• ISSN: 1948-5182; 1948-5182
• DOI: 10.4254/wjh.v2.i1.32

AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,Egypt.Fifteen wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal controls.Laboratory investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn’t express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and p27.Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC(P<0.01) to HCC(P<0.001) cases;meanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity.The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases.Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC;while,Cyclin E may be a useful marker for monitoring tumor behavior.p21 and p27 can be used as predictive markers for HCC.Furthermore,higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.