Ann Surg Treat Res.  2015 Jul;89(1):9-16. 10.4174/astr.2015.89.1.9.

CD44 expression in patients with combined hepatocellular cholangiocarcinoma

• Kim R
• Kim SB
• Cho EH
• Park SH
• Park SB
• Hong SK
• Chae G

• KMID: 2047708
• DOI: http://doi.org/10.4174/astr.2015.89.1.9

Abstract

PURPOSE
Combined hepatocellular cholangiocarcinoma (ChC) is a rare type of primary liver cancer, which is thought to have a poorer prognosis than hepatocellular carcinoma (HCC). Cancer stem cells are associated with tumorigenesis, tumor progression, recurrence, metastasis, and poor prognosis in several malignancies including HCC. The aim of this study was to investigate the expression pattern of cancer stem cell markers in ChC and HCC, and to evaluate whether this pattern correlated to patient prognosis.
METHODS
Thirteen patients who underwent curative hepatic resection for ChC and 13 patients who underwent curative hepatic resection for HCC (matched control cases) were included. Immunohistochemical staining for cancer stem cell markers (cytokeratin [CK]7, CK19, C-kit, cluster of differentiation [CD] 44, CD133, and epithelial cell adhesion molecule) was performed and clinical outcomes were analyzed retrospectively.
RESULTS
There was no significant difference in cancer stem cell marker expression between ChC and HCC. In ChC, the group that expressed CD44 showed earlier recurrence than the group that did not express CD44 (P = 0.040).
CONCLUSION
The expression of cancer stem cell markers in ChC did not show a different pattern compared to that found in HCC. The expression of cancer stem cell marker CD44 was associated with poor prognosis in patients with ChC.

Keyword

Hepatocellular carcinoma; Cholangiocarcinoma; Neoplastic stem cells; Cluster of Differentiation 44 (CD44)

MeSH Terms

Carcinogenesis
Carcinoma, Hepatocellular
Cholangiocarcinoma*
Epithelial Cells
Humans
Liver Neoplasms
Neoplasm Metastasis
Neoplastic Stem Cells
Prognosis
Recurrence
Retrospective Studies

Figure

• 

  Fig. 1 Recurrence-free survival analysis between ChC and HCC. ChC (solid line, n = 13) showed a significantly earlier recurrence than 1:1 matched HCC (dotted line, n = 13). ChC, combined hepatocellular cholangiocarcinoma; HCC, hepatocellular carcinoma.

• 

  Fig. 2 (A) Immunohistochemical staining of ChC (×100). Paraffin-embedded sections of ChC were immunostained in the cytoplasm with cytokeratin 19 antibodies (brown color, arrow). Slides were then counterstained with hematoxylin. (B) Immunohistochemical staining of ChC (×400). Paraffin-embedded sections of ChC were immunostained in the cytoplasm with CD44 antibodies (brown color, arrow). Slides were then counterstained with hematoxylin. (C) Immunohistochemical staining of ChC (×400). Paraffin-embedded sections of ChC were immunostained in the cytoplasm with EpCAM antibodies (brown color, arrow). Slides were then counterstained with hematoxylin. ChC, combined hepatocellular cholangiocarcinoma; EpCAM, epithelial cell adhesion molecule.

• 

  Fig. 3 Recurrence-free survival analysis between the CD44 expressed positive group and unexpressed group in ChC. The CD44 expressed group (solid line, n = 3) showed a significantly earlier recurrence than unexpressed group (dotted line, n = 10). ChC, combined hepatocellular cholangiocarcinoma; CD44, cluster of differentiation 44.

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