@article{oai:niigata-u.repo.nii.ac.jp:00006352,
 author = {WAKAI, Toshifumi and WATANABE, Hidenobu and SHIRAI, Yoshio and HATAKEYAMA, Katsuyoshi},
 issue = {2},
 journal = {Acta medica et biologica, Acta medica et biologica},
 month = {Jun},
 note = {BACKGROUND : No objective definition of p53 protein overexpression is found for hepatocellular carcinoma (HCC) in previous literature. Therefore, data on p53 status differ among investigators. The aim of this paper is to form an objective definition of p53 overexpression in HCC and assess the relationship between p53 overexpression and clinicopathological factors. METHODS : Two p53-specific monoclonal antibodies, PAb1801 and DO7,were used to compare p53 protein expression in 91 HCCs and its adjacent non-neoplastic liver tissues (91 patients), six adenomatous hyperplasias (2 patients), and 45 non-neoplastic liver tissues without tumor (45 patients). The p53 labeling index (LI) of each lesion was expressed as the number of p53 positive cells for more than 1,000 cells (range, 1006-1102 cells) in areas which counted the greatest number of positive cells in a homogeneous histological pattern. RESULTS : Of the 136 patients, 6 patients with cirrhosis and 4 patients with chronic active hepatitis showed p53-positive cells in non-neoplastic hepatocytes with DO7,but no PAb1801 positive cells were found in non-neoplastic hepatocytes in any of the cases. DO7-p53 LI of non-neoplastic hepatocytes in areas with p53-positive cells was less than 1 percent (mean±SD, 0.4±0.2%). Twenty-nine (32%) of 91 HCCs showed more than 1% p53 LI (p53 LI>1%) with either PAb1801 or DO7. The p53 LI>1% was observed in 5% (1/20) of well differentiated HCC, 33% (20/60) of moderately differentiated HCC, and 72.7% (8/11) of poorly and undifferentiated HCC. The ratio of p53 LI>1% was more frequent in patients with serological hepatitis B and/or C viral markers than in patients without these markers (P=0.003), but did not correlate with other clinicopathological factors including tumor size, portal invasion or intrahepatic metastasis. The p53 LI>1% in moderately differentiated HCCs showed a positive correlation with Ki-67 labeling index (P<0.03). CONCLUSIONS : p53 overexpression can be defined as greater than 1 percent of p53 LI, and is strongly related to viral chronic infection disease (HBV and/or HCV) and to cell proliferative activity of moderately differentiated HCCs.},
 pages = {49--60},
 title = {Overexpression of p53 Protein in Hepatocellular Carcinoma : Its Definition and Correlation with Viral Infection},
 volume = {47},
 year = {1999}
}