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Characterization of EGFR family gene aberrations in cholangiocarcinoma

  • Authors:
    • Xiaoqing Yang
    • Weishan Wang
    • Chunni Wang
    • Lin Wang
    • Muyi Yang
    • Mei Qi
    • Hong Su
    • Xiubin Sun
    • Zhiyan Liu
    • Juan Zhang
    • Xiaomin Qin
    • Bo Han

  • View Affiliations

  • Published online on: June 13, 2014     https://doi.org/10.3892/or.2014.3261
  • Pages: 700-708
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Abstract

Cholangiocarcinoma (CCA) is a highly lethal malignancy of the biliary tract with very few treatment options. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER2) have been considered as potential therapeutic targets in CCA. In the present study, we attempted to clarify the clinicopathological significance of all EGFR family members, EGFR, HER2, HER3 and HER4, across the full spectrum of CCAs. Immunohistochemistry and FISH were performed to validate expressions and genetic aberrations of these molecules retrospectively in 175 CCA patients. EGFR, HER3 and HER4 were overexpressed in 20 (30.8%), 8 (12.3%) and 41 (63.1%) of the 65 intrahepatic cholangiocarcinomas (IHCCs), and in 23 (20.9%), 13 (11.8%) and 62 (56.4%) of the 110 extrahepatic cholangiocarcinomas (EHCCs), respectively. Overexpression of HER2 was exclusively identified in EHCCs, among which the rate was 4.5% (5/110). A significant association was identified between EGFR amplification and EGFR overexpression (P=0.002). Similarly, HER2 amplification was strongly associated with HER2 overexpression (P<0.001). Multivariate analysis suggested that EGFR overexpression is an independent prognostic factor in IHCC, but not in EHCC cases [HR (95% CI): 3.689 (1.253-10.587), P=0.018]. Notably, for the first time, we demonstrated HER4 expression is a prognostic factor in EGFR-negative IHCC patients. In vitro data further suggested a tumor-suppressor role of HER4 in CCA. siRNA knockdown of HER4 significantly increased RBE cell migration and invasion. By contrast, HER4 overexpression decreased proliferation of HuCCT-1 cells and their migratory and invasive capacity. In summary, our results revealed expression of the EGFR family members in CCA development and progression. CCAs differentially express HER2 protein based on tumor location. HER4 expression status allows stratification of CCA patients into different survival categories.
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August-2014
Volume 32 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Yang X, Wang W, Wang C, Wang L, Yang M, Qi M, Su H, Sun X, Liu Z, Zhang J, Zhang J, et al: Characterization of EGFR family gene aberrations in cholangiocarcinoma. Oncol Rep 32: 700-708, 2014.
APA
Yang, X., Wang, W., Wang, C., Wang, L., Yang, M., Qi, M. ... Han, B. (2014). Characterization of EGFR family gene aberrations in cholangiocarcinoma. Oncology Reports, 32, 700-708. https://doi.org/10.3892/or.2014.3261
MLA
Yang, X., Wang, W., Wang, C., Wang, L., Yang, M., Qi, M., Su, H., Sun, X., Liu, Z., Zhang, J., Qin, X., Han, B."Characterization of EGFR family gene aberrations in cholangiocarcinoma". Oncology Reports 32.2 (2014): 700-708.
Chicago
Yang, X., Wang, W., Wang, C., Wang, L., Yang, M., Qi, M., Su, H., Sun, X., Liu, Z., Zhang, J., Qin, X., Han, B."Characterization of EGFR family gene aberrations in cholangiocarcinoma". Oncology Reports 32, no. 2 (2014): 700-708. https://doi.org/10.3892/or.2014.3261