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J Surg Res. 2014 Nov;192(1):117-23. doi: 10.1016/j.jss.2014.05.017. Epub 2014 May 10.

Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma.

Author information

1
Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France. Electronic address: laurent.sulpice@chu-rennes.fr.
2
Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France.
3
Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Service d'Anatomie et Cytologie Pathologiques, CHU Rennes, Rennes, France.
4
Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Centre Régional de Lutte contre le Cancer, Rennes, France.
5
Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France.
6
Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France.

Abstract

BACKGROUND:

Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC.

METHODS:

Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes.

RESULTS:

Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3-5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2-4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035).

CONCLUSIONS:

Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment.

KEYWORDS:

Biomarkers; Intrahepatic cholangiocarcinoma; Prognosis

PMID:
24909871
DOI:
10.1016/j.jss.2014.05.017
[Indexed for MEDLINE]
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