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Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma.

Abstract

To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the p53 oncoprotein in hepatitis B virus (HBV)/HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma (HCC). We studied needle liver biopsies from 107 patients with cirrhosis and no HCC (52 HBV, 55 HCV) who had been assessed for protocol studies, and 57 cirrhotic patients with HCC (40 HBV, 17 HCV). We evaluated small and large cell dysplastic changes along with the expression of Ki-67 and p53 by immunohistochemistry. The labelling index (LI) was defined as the proportion (%) of positive-stained nuclei of the 500 measured. Large and small cell dysplastic changes were observed in 12 and 9% of specimens respectively. Only small cell changes were associated with Ki-67 expression. Ki-67 LI was 5.50 +/- 5.7 in cirrhosis (13.90 +/- 3.84 in those with small cell dysplastic changes vs 4.64 +/- 4.98 in those without, P < 0.01), 10.2 +/- 5.95 in cirrhosis with HCC (P < 0.05) and 18.56 +/- 10 in HCC (P < 0.01). Neither the presence of small cell dysplastic changes nor the expression of Ki-67 was related to severity or aetiology of cirrhosis. Expression of p53 was observed in 30% of the non-tumorous and in 53% of the neoplastic tissue obtained from patients with HCC, with no differences between HCV and HBV. Ki-67 and p53 expression was associated with the tumour grade (P < 0.001). Our observations clearly demonstrate the association between the proliferation activity and the morphological changes in the cirrhotic liver from the non-dysplastic to dysplastic lesion to HCC. They also support the hypothesis that p53 alterations are a rather late event in carcinogenesis and related to HCC grade. And finally, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the chronic viral infection.

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  • Authors+Show Affiliations

    ,

    Second Department of Medicine, Athens University, Athens, Greece. koskinas@ath.forthnet.gr

    , , , ,

    Source

    Journal of viral hepatitis 12:6 2005 Nov pg 635-41

    MeSH

    Adult
    Aged
    Carcinoma, Hepatocellular
    Female
    Hepacivirus
    Hepatitis B
    Hepatitis B virus
    Hepatitis C
    Humans
    Ki-67 Antigen
    Liver
    Liver Cirrhosis
    Liver Neoplasms
    Male
    Middle Aged
    Tumor Suppressor Protein p53

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    16255765

    Citation

    Koskinas, J, et al. "Hepatic Expression of the Proliferative Marker Ki-67 and P53 Protein in HBV or HCV Cirrhosis in Relation to Dysplastic Liver Cell Changes and Hepatocellular Carcinoma." Journal of Viral Hepatitis, vol. 12, no. 6, 2005, pp. 635-41.
    Koskinas J, Petraki K, Kavantzas N, et al. Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma. J Viral Hepat. 2005;12(6):635-41.
    Koskinas, J., Petraki, K., Kavantzas, N., Rapti, I., Kountouras, D., & Hadziyannis, S. (2005). Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma. Journal of Viral Hepatitis, 12(6), pp. 635-41.
    Koskinas J, et al. Hepatic Expression of the Proliferative Marker Ki-67 and P53 Protein in HBV or HCV Cirrhosis in Relation to Dysplastic Liver Cell Changes and Hepatocellular Carcinoma. J Viral Hepat. 2005;12(6):635-41. PubMed PMID: 16255765.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma. AU - Koskinas,J, AU - Petraki,K, AU - Kavantzas,N, AU - Rapti,I, AU - Kountouras,D, AU - Hadziyannis,S, PY - 2005/11/1/pubmed PY - 2005/12/13/medline PY - 2005/11/1/entrez SP - 635 EP - 41 JF - Journal of viral hepatitis JO - J. Viral Hepat. VL - 12 IS - 6 N2 - To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the p53 oncoprotein in hepatitis B virus (HBV)/HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma (HCC). We studied needle liver biopsies from 107 patients with cirrhosis and no HCC (52 HBV, 55 HCV) who had been assessed for protocol studies, and 57 cirrhotic patients with HCC (40 HBV, 17 HCV). We evaluated small and large cell dysplastic changes along with the expression of Ki-67 and p53 by immunohistochemistry. The labelling index (LI) was defined as the proportion (%) of positive-stained nuclei of the 500 measured. Large and small cell dysplastic changes were observed in 12 and 9% of specimens respectively. Only small cell changes were associated with Ki-67 expression. Ki-67 LI was 5.50 +/- 5.7 in cirrhosis (13.90 +/- 3.84 in those with small cell dysplastic changes vs 4.64 +/- 4.98 in those without, P < 0.01), 10.2 +/- 5.95 in cirrhosis with HCC (P < 0.05) and 18.56 +/- 10 in HCC (P < 0.01). Neither the presence of small cell dysplastic changes nor the expression of Ki-67 was related to severity or aetiology of cirrhosis. Expression of p53 was observed in 30% of the non-tumorous and in 53% of the neoplastic tissue obtained from patients with HCC, with no differences between HCV and HBV. Ki-67 and p53 expression was associated with the tumour grade (P < 0.001). Our observations clearly demonstrate the association between the proliferation activity and the morphological changes in the cirrhotic liver from the non-dysplastic to dysplastic lesion to HCC. They also support the hypothesis that p53 alterations are a rather late event in carcinogenesis and related to HCC grade. And finally, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the chronic viral infection. SN - 1352-0504 UR - https://www.unboundmedicine.com/medline/citation/16255765/Hepatic_expression_of_the_proliferative_marker_Ki_67_and_p53_protein_in_HBV_or_HCV_cirrhosis_in_relation_to_dysplastic_liver_cell_changes_and_hepatocellular_carcinoma_ L2 - https://doi.org/10.1111/j.1365-2893.2005.00635.x DB - PRIME DP - Unbound Medicine ER -