Hepatic Expression of the Proliferative Marker Ki-67 and cell cycle p53 Protein in chronic hepatitis C (A histopathological and immunohistochemical study)

摘要

Aim and background: To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the cell cycle marker p53 oncoprotein in chronic hepatitis C in relation to the advanced stages of liver fibrosis in HCV positive Egyptian patients . Material & Methods: Paraffin-embedded liver biopsy specimens were studied from 21 untreated patients with chronic HCV infection. All patients were HCV antibody positive, as determined by a commercially available enzyme-linked immunosorbent assay kit. Patients having other etiologies for chronic liver disease including HBV infection were not included in this study. Liver biopsies were obtained percutaneous. All biopsies were fixed in formalin, embedded in paraffin, and sectioned by microtome with a thickness of 5 μm. Routine specimen processing involved staining slides with hematoxylin and eosin (5 levels), Masson's trichrome stain (5 levels), for a total of 10 levels per specimen All levels were screened. All specimens were examined by two pathologists, and classified by consensus for all abnormal histological findings. The histological activity index (or histological grade) was determined using Ishak grading scheme22 expressed as a semiquantitative score for portal inflammation (0-4), lobular activity sporadic lytic foci (0-4) and parenchymal confluent necrosis (0-6), and piecemeal necrosis(0-4). The extent of fibrosis (or histological stage) was determined using Ishak score (0-6). Steatosis was scored according to Keliner et al 2005 , from grade 0 to 3; where S0 = no steatosis or less than 5% (low or medium power evaluation) of parenchymal involvement by fatty changes, S1 (mild) = 5%-33%, S2 (moderate) = >33%-66% and S3 (severe) > 66% of the hepatocytes are involved by fatty changes. Expression of p53 and Ki67 were determined by immunohistochemistry, using avidin-biotin-peroxidase. Results: Liver histology: The studied group (n = 21) involved 16 males and 5 females (male to female ratio 3.3:1). The histopathological findings of HCV infection, including portal lymphoid infiltration, periportal piecemeal necrosis, lymphocyte infiltration of the lobules, hepatocellular necrosis, steatosis and fibrosis, were studies. The age ranged from 31 to 59 years old with mean of 44.86 ± 8.74, males 76.2%, females 23.8% .P53 expression was positive in 52.4% and negative in 47.6%. cytoplasmic localization dominated over nuclear expression. Ki 67 was negative in 81% of cases and positive in19% of cases, all cases in stage 6 were positive for p53 while there were no difference in the other stages of fibrosis, and this relation was statistically significant. There was no relation between the grade of necro-inflammation and the expression of p53,