Immunohistologic attempt to find carcinogenesis from hepatic progenitor cell in hepatocellular carcinoma.
OBJECTIVE
To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens.


METHODS
Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene.


RESULTS
CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation.


CONCLUSIONS
These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis.
Yamamoto
Takatsugu
T
Department of Surgery, Ishikiri Seiki Hospital, Osaka, Japan. takatsugu@misc.med.osaka-cu.ac.jp
Uenishi
Takahiro
T
Ogawa
Masao
M
Ichikawa
Tsuyoshi
T
Hai
Seikan
S
Sakabe
Katsu
K
Tanaka
Shogo
S
Kato
Hiroshi
H
Mikami
Shinichi
S
Ikebe
Takashi
T
Tanaka
Hiromu
H
Ito
Satoru
S
Kaneda
Kenji
K
Hirohashi
Kazuhiro
K
Kubo
Shoji
S
D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D016009:Chi-Square Distribution; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate
D007633:Keratins