Please use this identifier to cite or link to this item: https://doi.org/10.1007/s00428-015-1745-4
Title: Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma
Authors: Srivastava, Supriya 
Thakkar, Bhavin 
Yeoh, Khay Guan 
Ho, Khek Yu 
Teh, Ming 
Soong, Richie 
Salto-Tellez, Manuel 
Keywords: Science & Technology
Life Sciences & Biomedicine
Pathology
CA-IX
HIF-1 alpha
Liver cancer
Prognosis
Survival
Wnt pathway
CARBONIC-ANHYDRASE-IX
HUMAN HEPATOMA-CELLS
INDUCIBLE FACTOR-I
BETA-CATENIN
NATURAL-HISTORY
TUMOR HYPOXIA
E-CADHERIN
MARKER
LIVER
HIF-1-ALPHA
Issue Date: 1-May-2015
Publisher: SPRINGER
Citation: Srivastava, Supriya, Thakkar, Bhavin, Yeoh, Khay Guan, Ho, Khek Yu, Teh, Ming, Soong, Richie, Salto-Tellez, Manuel (2015-05-01). Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma. VIRCHOWS ARCHIV 466 (5) : 541-548. ScholarBank@NUS Repository. https://doi.org/10.1007/s00428-015-1745-4
Abstract: © 2015, Springer-Verlag Berlin Heidelberg. In the development and progression of hepatocellular carcinoma, tumor hypoxia plays an important role, as does activation of the Wnt pathway. The aim of this study was to characterize the expression and interrelationship between hypoxia and Wnt-pathway-associated proteins as prognostic factors for hepatocellular carcinoma. Expression of HIF-1α, CA-IX, E-cadherin, β-catenin, and Ki-67 was assessed by immunohistochemistry in 179 primary hepatocellular carcinoma cases. Univariate and multivariate analyses were performed to assess the relationship between the clinicopathological factors, protein expression, overall survival (OS), and recurrence-free survival (RFS). By univariate analysis, tumor stage, size, satellitosis, and vascular invasion were confirmed as prognostic factors for worse OS and RFS. High expression of HIF-1α, CA-IX, β-catenin, Ki-67, and E-cadherin was observed in 60, 15, 64, 8, and 64 % of tumors, respectively, and this was significantly associated with poor OS. CA-IX, HIF-1α, and E-cadherin were independent predictors of poor prognosis. We stratified 169 patients into four groups according to the expression level of hypoxia and Wnt pathway markers. The group with high expression of both hypoxia and Wnt-pathway-associated proteins showed worst OS. The poor survival of this group was also significant in patients with early stage disease and tumor size of less than 5 cm (p < 0.05). We identified a subgroup of hepatocellular carcinoma patients with high expression of both hypoxia and Wnt pathway proteins and found this predictive of poor survival. The therapeutic options for this group might need to be revisited.
Source Title: VIRCHOWS ARCHIV
URI: https://scholarbank.nus.edu.sg/handle/10635/184185
ISSN: 09456317
14322307
DOI: 10.1007/s00428-015-1745-4
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