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ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma
  1. Katsumi Terashita1,
  2. Makoto Chuma1,2,
  3. Yutaka Hatanaka3,
  4. Kanako Hatanaka3,
  5. Tomoko Mitsuhashi3,
  6. Hideki Yokoo4,
  7. Takumi Ohmura5,
  8. Hiroyuki Ishizu6,
  9. Shunji Muraoka7,
  10. Atsushi Nagasaka8,
  11. Takahiro Tsuji9,
  12. Yoshiya Yamamoto10,
  13. Nobuaki Kurauchi11,
  14. Norihiko Shimoyama12,
  15. Hidenori Toyoda13,
  16. Takashi Kumada13,
  17. Yuji Kaneoka14,
  18. Atsuyuki Maeda14,
  19. Koji Ogawa1,
  20. Mitsuteru Natsuizaka1,
  21. Hirofumi Kamachi4,
  22. Tatsuhiko Kakisaka4,
  23. Toshiya Kamiyama4,
  24. Akinobu Taketomi4,
  25. Yoshihiro Matsuno3,
  26. Naoya Sakamoto1
  1. 1Departments of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
  2. 2Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
  3. 3Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
  4. 4Department of Gastroenterological Surgery I, Hokkaido University Hospital, Sapporo, Japan
  5. 5Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Japan
  6. 6Department of Surgery, Sapporo-Kosei General Hospital, Sapporo, Japan
  7. 7Department of Pathology, Sapporo-Kosei General Hospital, Sapporo, Japan
  8. 8Department of Gastroenterology, Sapporo Municipal Hospital, Sapporo, Japan
  9. 9Department of Pathology, Sapporo Municipal Hospital, Sapporo, Japan
  10. 10Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan
  11. 11Department of Surgery, Hakodate Municipal Hospital, Hakodate, Japan
  12. 12Department of Pathology, Hakodate Municipal Hospital, Hakodate, Japan
  13. 13Departments of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
  14. 14Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
  1. Correspondence to Dr Makoto Chuma, Department of Gastroenterology and Hepatology, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan; chuma{at}yokohama-cu.ac.jp

Abstract

Background/Aim Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial–mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins.

Methods We immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated.

Results ZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan–Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival.

Conclusions ZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC.

  • LIVER CANCER
  • IMMUNOHISTOCHEMISTRY
  • CHOLANGIOCARCINOMA

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