Characterizing the activation of the Wnt signaling pathway in hilar cholangiocarcinoma using a tissue microarray approach

  • W. Chen Sun Yat-sen University, China.
  • J. Liang Sun Yat-sen University, China.
  • L. Huang Sun Yat-sen University, China.
  • J. Cai Sun Yat-sen University, China.
  • Y. Lei Sun Yat-sen University, China.
  • J. Lai Sun Yat-sen University, China.
  • L. Liang Sun Yat-sen University, China.
  • K. Zhang | zhangkunsong@263.net Sun Yat-sen University, China.

Abstract

Hilar cholangiocarcinoma (HCCA) is an invasive hepatic malignancy that is difficult to biopsy; therefore, novel markers of HCCA prognosis are needed. Here, the level of canonical Wnt activation in patients with HCCA, intrahepatic cholangiocarcinoma (IHCC), and congenital choledochal cysts (CCC) was compared to understand the role of Wnt signaling in HCCA. Pathology specimens from HCCA (n=129), IHCC (n=31), and CCC (n=45) patients were used to construct tissue microarrays. Wnt2, Wnt3, β-catenin, TCF4, c-Myc, and cyclin D1 were detected by immunohistochemistry. Parallel correlation analysis was used to analyze differences in protein levels between the HCCA, IHCC, and CCC groups. Univariate and multivariate analyses were used to determine independent predictors of successful resection and prognosis in the HCCA group. The protein levels of Wnt2, β-catenin, TCF4, c-Myc, and cyclin D1 were significantly higher in HCCA compared to IHHC or CCC. Wnt signaling activation (Wnt2+, Wnt3+, nuclear β-catenin+, nuclear TCF4+) was significantly greater in HCCA tissues than CCC tissues. Univariable analyses indicated that expression of cyclin D1 as well as Wnt signaling activation, and partial Wnt activation (Wnt2+ or Wnt3+ and nuclear β-catenin+ or nuclear TCF4+) predicted successful resection, but only cyclin D1 expression remained significant in multivariable analyses. Only partial Wnt activation was an independent predictor of survival time. Proteins in the canonical Wnt signaling pathway were present at higher levels in HCCA and correlated with tumor resecility and patient prognosis. These results suggest that Wnt pathway analysis may be a useful marker for clinical outcome in HCCA.

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Published
2016-02-09
Section
Original Papers
Supporting Agencies
Medical Scientific Research Foundation of Guangdong Province, Guangdong Natural Science Foundation.
Keywords:
Hilar cholangiocarcinoma, Wnt signaling pathway, tissue microarray, β-catenin, c-Myc, cyclin D1.
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How to Cite
Chen, W., Liang, J., Huang, L., Cai, J., Lei, Y., Lai, J., Liang, L., & Zhang, K. (2016). Characterizing the activation of the Wnt signaling pathway in hilar cholangiocarcinoma using a tissue microarray approach. European Journal of Histochemistry, 60(1). https://doi.org/10.4081/ejh.2016.2536