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The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type
  1. Jun Akiba1,
  2. Osamu Nakashima2,
  3. Satoshi Hattori3,
  4. Yoshiki Naito1,
  5. Hironori Kusano1,
  6. Reiichiro Kondo1,
  7. Masamichi Nakayama1,
  8. Ken Tanikawa1,
  9. Keita Todoroki1,
  10. Yumi Umeno1,
  11. Ken Nakamura1,
  12. Sakiko Sanada1,
  13. Rin Yamaguchi1,
  14. Sachiko Ogasawara1,
  15. Hirohisa Yano1
  1. 1Department of Pathology, Kurume University School of Medicine, Kurume, Japan
  2. 2Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
  3. 3Biostatistics Center, Kurume University, Kurume, Japan
  1. Correspondence to Dr Jun Akiba, Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan; akiba{at}


Aims The WHO classification describes that combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell subtype (CHC-INT) is composed of tumour cells with features intermediate between hepatocytes and cholangiocytes. However, we previously reported that CHC-INT showed a high positive rate of biliary markers, but the expression of hepatocyte paraffin (HepPar)-1 was low. In this study, we examined the expression of other hepatocyte markers, such as arginase-1 (Arg-1), keratin (K) 8 and K18 in CHC-INT in order to examine the utility of pathological diagnosis in CHC-INT.

Methods We performed immunohistochemistry (IHC) of Arg-1, K8 and K18 using 32 previously diagnosed as CHC-INT. Immunoreactivity was evaluated with grading from 0 to 4 according to the distribution area of positive cells. The obtained findings of Arg-1, K8 and K18 were compared with those of K7, K19 and HepPar-1.

Results Out of the 32 cases, 22 (68.8%) cases were positive for Arg-1. Twenty-five (78.1%) were positive for K8. The IHC scores of Arg-1 and K8 were significantly higher than those of HepPar-1, but significantly lower than those of K7 and K19. The K18 expression was widely observed in all cases (100%). The IHC score of Arg-1 and K8 in CHC-INT was intermediate between hepatocellular carcinoma and cholangiocarcinoma.

Conclusions Arg-1 and K8 were good markers to identify intermediate cells between hepatocytes and cholangiocytes. These can be useful markers for pathological diagnosis of CHC-INT, which usually has wide histological diversities, in combination with other hepatocytic and/or cholangiocytic markers.


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