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Hepatocellular Carcinoma Expressing Cholangiocyte Phenotype Is a Novel Subtype with Highly Aggressive Behavior

Annals of Surgical Oncology volume 18, pages 2210–2217 (2011)Cite this article

Abstract

Background

The pathobiological features and surgical outcomes of patients with classical hepatocellular carcinoma (HCC)-expressing cholangiocyte markers that we named dual-phenotype HCC (DPHCC) remain unclear. The purpose of this study was to assess the association between the phenotype and surgicopathologic features of DPHCC.

Methods

A retrospective single-center study was performed on the surgicopathologic features of DPHCC from 1530 consecutive surgical specimens. Immunohistochemical staining was performed with antibodies to hepatocytes (Hep Par 1/pCEA) and cholangiocytes (cytokeratin 19 [CK19]/mucin core protein-1 [MUC-1]).

Results

DPHCC accounted for 10.1% (n = 155) of total HCCs. The serum alfa-fetoprotein and CA19-9 were elevated in 87.7% (n = 136) and 20.7% (n = 32) of patients, respectively; the former had close correlation with the immunostaining of CK19 (P < 0.01). The combination of immunostaining intensities of CK19 and MUC-1 was significantly associated with tumor size, microvascular invasion, and satellite nodule formation (P < 0.05–0.01). Compared to patients with pure HCC, those with DPHCC had significantly lower overall survival (30.4 ± 3.7 vs. 43.6 ± 3.9 months, P < 0.05) and recurrence-free survival (13.2 ± 2.0 vs. 23.4 ± 2.5 months, P < 0.01), respectively. Multivariate Cox regression analyses identified CK19-positive expression to be an independent prognostic factor for both overall survival and recurrence-free survival.

Conclusions

DPHCC is a novel surgicopathologic entity that has a highly aggressive behavior and worse postoperative prognosis than pure HCC. Because the morphological features between DPHCC and conventional HCC overlap, we recommend that CK19 be routinely used in the pathological diagnosis of HCC for screening DPHCC.

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Acknowledgment

This study was supported by the National Natural Science Foundation of China (grants 30872506, 81072026).

Disclosure

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

    Xin-Yuan Lu MD, Hui Dong MD, PhD, Zhen Zhu MD & Wen-Ming Cong MD, PhD

  2. Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

    Tao Xi MD, Wan-Yee Lau MD, PhD, Feng Shen MD, PhD & Meng-Chao Wu MD

  3. Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

    Wan-Yee Lau MD, PhD

Authors
  1. Xin-Yuan Lu MD
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  2. Tao Xi MD
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  3. Wan-Yee Lau MD, PhD
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  4. Hui Dong MD, PhD
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  5. Zhen Zhu MD
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  6. Feng Shen MD, PhD
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  7. Meng-Chao Wu MD
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  8. Wen-Ming Cong MD, PhD
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Corresponding author

Correspondence to Wen-Ming Cong MD, PhD.

Additional information

Xin-Yuan Lu and Tao Xi contributed equally to this work.

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Lu, XY., Xi, T., Lau, WY. et al. Hepatocellular Carcinoma Expressing Cholangiocyte Phenotype Is a Novel Subtype with Highly Aggressive Behavior. Ann Surg Oncol 18, 2210–2217 (2011). https://doi.org/10.1245/s10434-011-1585-7

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  • DOI: https://doi.org/10.1245/s10434-011-1585-7

Keywords

  • Overall Survival
  • Tumor Thrombus
  • Capsular Invasion
  • CK19 Expression
  • Hepatic Progenitor Cell