Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: comprehensive immunohistochemical study using a tissue microarray.

Abstract

BACKGROUND:

Epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial-mesenchymal transition is proposed to occur in various developmental processes and cancer progression. 'Cadherin switch', a process in which cells shift to express different isoforms of the cadherin transmembrane protein and usually refers to a switch from the expression of E-cadherin to N-cadherin, is one aspect of EMT and can have a profound effect on tumour invasion/metastasis. The aim of this study was to investigate the clinicopathological significance of EMT-related proteins and cadherin switch in extrahepatic cholangiocarcinoma (EHCC).

METHODS:

We investigated the association between altered expression of 12 EMT-related proteins and clinical outcomes in patients with EHCC (n=117) using immunohistochemistry on tissue microarrays.

RESULTS:

Univariate and multivariate analyses revealed that, in addition to N classification (P=0.0420), the expression of E-cadherin (P=0.0208), N-cadherin (P=0.0038) and S100A4 (P=0.0157) was each an independent and a significant prognostic factor. We also demonstrated that cadherin switch was independently associated with poor prognosis (P=0.0143) in patients with EHCC.

CONCLUSIONS:

These results may provide novel information for selection of patients with EHCC who require adjuvant therapy and strict surveillance.

• Authors: T Nitta, T Mitsuhashi, Y Hatanaka, M Miyamoto, K Oba, T Tsuchikawa, Y Suzuki, K C Hatanaka, S Hirano, Y Matsuno
• Journal: British journal of cancer (Br J Cancer) Vol. 111 Issue 7 Pg. 1363-72 (Sep 23 2014) ISSN: 1532-1827 [Electronic] England
• PMID: 25077440 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Biomarkers, Tumor
• CDH1 protein, human
• CDH2 protein, human
• Cadherins

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, CD (metabolism)
• Bile Duct Neoplasms (metabolism, mortality, pathology)
• Bile Ducts, Extrahepatic (metabolism, pathology)
• Bile Ducts, Intrahepatic (metabolism, pathology)
• Biomarkers, Tumor (metabolism)
• Cadherins (metabolism)
• Cell Line, Tumor
• Cholangiocarcinoma (metabolism, mortality, pathology)
• Epithelial-Mesenchymal Transition
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Prognosis
• Tissue Array Analysis