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Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma

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Abstract

Expression of phenotype markers of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) in HCC and CC components of 20 combined hepatocellular and cholangiocarcinomas (CHCs) of the liver was investigated immunohistochemically. Both HCC and CC components of all CHCs expressed at least one of the CC phenotype markers [cytokeratin (CK)-7, CK-19, and carbohydrate (CA) 19-9]. HCC components in 90% of CHCs and CC components in 95% of CHCs expressed at least one of these CC phenotype markers in more than 40% of cancer cells. HCC components in all CHCs expressed at least one of the HCC phenotype markers [hepatocyte antigen (HA), α-fetoprotein (AFP), and canalicular carcinoembryonic antigen]. HCC components in 90% of CHCs and CC components in 75% of CHCs expressed HA, AFP, or both. HCC components in 75% of CHCs and CC components in 60% of CHCs expressed HA, AFP, or both in more than 10% of cancer cells. The present results show that both HCC and CC components of most of the CHCs expressed both HCC and CC phenotypes, supporting the hypothesis that CHC originates from a hepatic progenitor cell capable of differentiating into hepatocytes and cholangiocytes.

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References

  1. Witteking C, Fischer HP, Ponchon (2000) Combined hepatocellular and cholangiocarcinoma. In: Hamilton SR, Aaltonen LA (eds) World Health Organization classification of tumours: pathology and genetics of tumours of the digestive system. IARC Press, Lyon, p 181

    Google Scholar 

  2. Maeda T, Adachi E, Kajiyama K, Sugimachi K, Tsuneyoshi M (1995) Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Hum Pathol 26:956–964

    Article  PubMed  CAS  Google Scholar 

  3. Yano Y, Yamamoto J, Kosuge T, Sakamoto Y, Yamasaki S, Shimada K, Ojima H, Sakamoto M, Takayama T, Makuuchi M (2003) Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases. Jpn J Clin Oncol 33:283–287

    Article  PubMed  Google Scholar 

  4. Zou H-Q, Yan L-N, Zeng Y, Yang J-Y, Luo H-Z, Liu J-W, Zhou L-X (2007) Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma. Hepatobiliary Pancreat Dis Int 6:161–165

    Google Scholar 

  5. Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L (1985) Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer (Phila) 55:124–135

    Article  CAS  Google Scholar 

  6. Taguchi J, Nakashima O, Tanaka M, Hisaka T, Takazawa T, Kojiro M (1996) A clinicopathological study on combined hepatocellular and cholangiocarcinoma. J Gastroenterol Hepatol 11:758–764

    Article  PubMed  CAS  Google Scholar 

  7. Ng IO, Shek TW, Nicholls J, Ma LT (1998) Combined hepatocellular-cholangiocarcinoma: a clinicopathological study. J Gastroenterol Hepatol 13:34–40

    Article  PubMed  CAS  Google Scholar 

  8. Tickoo SK, Zee SY, Obiekwe S, Xiao H, Koea J, Robiou C, Blumgart LH, Jarnagin W, Ladanyi M, Klimstra DS (2002) Combined hepatocellular-cholangiocarcinoma. A histopathologic, immunohistochemical, and in situ hybridization study. Am J Surg Pathol 26:989–997

    Article  PubMed  Google Scholar 

  9. Uenishi T, Kubo S, Yamamoto T, Shuto T, Ogawa M, Tanaka H, Tanaka S, Kaneda K, Hirohashi K (2003) Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence. Cancer Sci 94:851–857

    Article  PubMed  CAS  Google Scholar 

  10. Durnez A, Verslype C, Nevens F, Fevery J, Aerts R, Pirenne J, Lesaffre E, Libbrecht L, Desmet V, Roskams T (2006) The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology (Oxf) 49:138–151

    Article  CAS  Google Scholar 

  11. Woo HG, Lee J-H, Yoon J-H, Kim CY, Lee H-S, Jang JJ, Yi N-J, Suh K-S, Lee KU, Park ES, Thorgeirsson SS, Kim YJ (2010) Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma. Cancer Res 70:3034–3041

    Article  PubMed  CAS  Google Scholar 

  12. Roskams T (2006) Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene 25:3818–3822

    Article  PubMed  CAS  Google Scholar 

  13. Yang X-R, Xu Y, Shi G-M, Fan J, Zhou J, Ji Y, Sun H-C, Qiu S-J, Yu B, Gao Q, He Y-Z, Qin W-Z, Chen R-X, Yang G-H, Wu B, Lu Q, Wu Z-Q, Tang Z-Y (2008) Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res 14:3850–3859

    Article  PubMed  CAS  Google Scholar 

  14. Jarnagin WR, Weber S, Tickoo SK, Koea JB, Obiekwe S, Fong Y, DeMatteo RP, Blumgart LH, Klimstra D (2002) Combined hepatocellular and cholangiocarcinoma. Cancer (Phila) 94:2040–2046

    Article  Google Scholar 

  15. Koh KC, Lee H, Choi MS, Lee JH, Paik SW, Yoo BC, Rhee JC, Cho JW, Park CK, Kim HJ (2005) Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma. Am J Surg 189:120–125

    Article  PubMed  Google Scholar 

  16. Lee W-S, Lee K-W, Heo J-S, Kim S-J, Choi S-H, Kim Y-I, Choi S-H, Kim Y-I, Joh J-W (2006) Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Surg Today 36:892–897

    Article  PubMed  Google Scholar 

  17. Chu PG, Ishizawa S, Wu E, Weiss LM (2002) Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD 10, and alpha-fetoprotein. Am J Surg Pathol 26:978–988

    Article  PubMed  Google Scholar 

  18. Lau SK, Prakash S, Geller SA, Alsabeh R (2002) Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol 33:1175–1181

    Article  PubMed  Google Scholar 

  19. Fan Z, van de Rijin M, Montogomery K, Rouse RV (2003) Hep Par1 antibody stain for the differential diagnosis of hepatocellular carcinoma: 676 tumors tested using tissue microarrays and conventional tissue sections. Mod Pathol 16:137–144

    Article  PubMed  Google Scholar 

  20. Kakar S, Muir T, Murphy LM, Lloyd RV, Burgart LJ (2003) Immunoreactivity of Hep Par 1 in hepatic and extrahepatic tumors and its correlation with albumin in situ hybridization in hepatocellular carcinoma. Am J Clin Pathol 119:361–366

    Article  PubMed  Google Scholar 

  21. Maeda T, Kajiyama K, Adachi E, Takenaka K, Sugimachi K, Tsuneyoshi M (1996) The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver. Mod Pathol 9:901–909

    PubMed  CAS  Google Scholar 

  22. Tsuji M, Kashihara T, Terada N, Mori H (1999) An immunohistochemical study of hepatic atypical adenomatous hyperplasia, hepatocellular carcinoma, and cholangiocarcinoma with α-fetoprotein, carcinoembryonic antigen, CA19-9, epithelial membrane antigen, and cytokeratins 18 and 19. Pathol Int 449:310–317

    Article  PubMed  CAS  Google Scholar 

  23. Ma CK, Zarbo RJ, Frierson HF, Lee MW (1993) Comparative immunohistochemical study of primary and metastatic carcinomas of the liver. Am J Clin Pathol 99:551–557

    PubMed  CAS  Google Scholar 

  24. Cazal-Hatem D, Rebouissou S, Bioulac-Sage P, Bluteau O, Blanché H, Franco D, Monges G, Belghiti J, Cunha AS, Laurent-Puig P, Degott C, Zucman-Rossi J (2004) Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas. J Hepatol 41:292–298

    Article  Google Scholar 

  25. Fujii H, Zhu XG, Matsumoto T, Inagaki M, Tokusashi Y, Miyokawa N, Fukusato T, Uekusa T, Takagaki T, Kadowaki N, Shirai T (2000) Genetic classification of combined hepatocellular-cholangiocarcinoma. Hum Pathol 31:1011–1017

    Article  PubMed  CAS  Google Scholar 

  26. Komuta M, Spee B, Vander Borght S, De Vos R, Verslype C, Aerts R, Yano H, Suzuki T, Matsuda M, Fujii H, Desmet VJ, Kojiro M, Roskams T (2008) Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology 47:1544–1556

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Mitsumaro Itoyama, Masaki Hata, Koji Yamanegi, Naoko Yamada, Hideki Ohyama, Hiroshi Hirano, Nobuyuki Terada & Keiji Nakasho

  2. Department of Pathology, National Hospital Organization, Osaka National Hospital, Osaka, Japan

    Mitsumaro Itoyama

  3. Department of Pathology, Nippon Steel Hirohata Hospital, Hyogo, Japan

    Hiroshi Hirano

Authors
  1. Mitsumaro Itoyama
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  2. Masaki Hata
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  3. Koji Yamanegi
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  4. Naoko Yamada
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  5. Hideki Ohyama
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  6. Hiroshi Hirano
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  7. Nobuyuki Terada
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  8. Keiji Nakasho
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Correspondence to Keiji Nakasho.

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Itoyama, M., Hata, M., Yamanegi, K. et al. Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma. Med Mol Morphol 45, 7–13 (2012). https://doi.org/10.1007/s00795-010-0534-z

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  • DOI: https://doi.org/10.1007/s00795-010-0534-z

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