J Pathol Transl Med.  2016 Jan;50(1):52-57. 10.4132/jptm.2015.10.09.

Immunohistochemical Expression and Clinical Significance of Suggested Stem Cell Markers in Hepatocellular Carcinoma

• Sung JJ
• Noh SJ
• Bae JS
• Park HS
• Jang KY
• Chung MJ
• Moon WS

• KMID: 2211401
• DOI: http://doi.org/10.4132/jptm.2015.10.09

Abstract

BACKGROUND
Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics.
METHODS
Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens.
RESULTS
EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated alpha-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, EpCAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively.
CONCLUSIONS
Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare.

Keyword

Carcinoma, hepatocellular; EpCAM protein; Cancer stem cells

MeSH Terms

alpha-Fetoproteins
Carcinoma, Hepatocellular*
Epithelial Cells
Humans
Keratin-19
Microvessels
Neoplasm Metastasis
Neoplastic Stem Cells
Recurrence
Stem Cells*
Survival Rate
Keratin-19
alpha-Fetoproteins

Figure

• 

  Fig. 1. (A) Membranous expression of epithelial cell adhesion molecule (EpCAM) in hepatocellular carcinoma cells. Bile duct epithelial cells also showed strong expression of EpCAM (arrow). (B) Tumor cells with cytoplasmic reactivity for keratin 19. Absence of CD133 (C) and CD56 (D) immunoreactivity in tumor cells (T). Note the positive immunoreactivity for CD133 and CD56 in bile ductular cells (arrows).

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