Liver, Pancreas, and Biliary Tractp16INK4 is inactivated by extensive CpG methylation in human hepatocellular carcinoma☆
Section snippets
Tissue samples
HCC tissue specimens were obtained from 60 individuals (48 men and 12 women), ranging in age between 29 and 75 years (mean age, 58 ± 12 years), undergoing surgical resection or biopsy. Eleven (18%) individuals were positive for hepatitis B surface antigen, 44 (73%) were positive for hepatitis C virus antibody, and 2 were positive for both viral markers. None had hereditary or systemic disorders. The size of the tumors varied from 1.5 to 16 cm (mean size, 5.0 ± 3.8 cm). Tissue samples were fixed
Immunohistochemistry
All normal livers and livers with benign hepatic diseases showed p16-positive nuclear immunostaining (Figure 1A).
Discussion
We chose to focus on primary HCC tissues because significant differences in the frequency of p16 inactivation have been shown between primary cancers and cultured cells.16, 17 Immunostaining showed that p16 expression was lost completely in approximately half of the HCCs examined, and the proportion of tumors with reduced p16 immunostaining increased according to the histological stage. There was no statistical association between the loss of p16 expression and etiologic factors in individuals
Acknowledgements
The authors thank N. Honda, T. Tsuchida, and H. Koizumi for technical assistance.
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Address requests for reprints to: Takafumi Ichida, M.D., Department of Internal Medicine III, Niigata University School of Medicine, Asahimachi-dori 1, Niigata City 951-8122, Japan. e-mail: [email protected]; fax: (81) 25-227-0776.