Bile ductular cell reaction with senescent hepatocytes in chronic viral hepatitis is lost during hepatocarcinogenesis

Authors: Ikeda, Hiroko; Sasaki, Motoko¹; Sato, Yasunori¹; Harada, Kenichi¹; Zen, Yoh²; Mitsui, Takeshi³; Nakanuma, Yasuni

Source: Pathology International, Volume 59, Number 7, July 2009 , pp. 471-478(8)

Publisher: Wiley-Blackwell

Abstract:

Cellular senescence is defined as irreversible cell arrest and could work as a safeguard against tumorigenesis. This mechanism was examined in chronic viral hepatitis-related hepatocarcinogenesis. By using surgical resected or wedge biopsied liver specimens from 87 chronic viral hepatitis patients in whom 35 neoplastic nodules (dysplastic nodules and hepatocellular carcinoma) were complicated, P21 expression and senescence-associated β galactosidase activity, a marker of senescence, were examined. All of these neoplastic nodules harbored portal tracts within the tumors. Hepatocytes expressing senescence markers and cytokeratin (CK)7-positive bile ductules including hepatic progenitor-like cells were increased in periseptal areas in cirrhosis. Interestingly, these cells appeared to form an anatomical complex that was completely lost in the periportal areas within the neoplastic nodules. In one-third of the neoplastic nodules, CK7-positive small neoplastic hepatocytes resembling hepatic progenitor cells proliferated zonally around the portal tracts. In conclusion, loss of a complex of senescent hepatocytes and ductular cell including hepatic progenitor-like cells in the periportal or periseptal areas may be associated with emergence of neoplastic hepatocytes and their proliferation followed by neoplastic nodules arising in liver cirrhosis. Zonal proliferation of CK7-positive small neoplastic hepatocytes resembling hepatic progenitor cells may develop during early hepatocarcinogenesis.

Keywords: cellular senescence; dysplastic nodule; hepatic progenitor cell; hepatocellular carcinoma; liver cirrhosis

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1440-1827.2009.02395.x

Affiliations: 1: Departments of Human Pathology and 2: Section of Diagnostic Pathology, Kanazawa University Hospital, Kanazawa and 3: Department of Surgery, Fukui Saiseikai Hospital, Fukui, Japan

Publication date: 2009-07-01

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