The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers

Angela Lamarca, Salvatore Galdy, Jorge Barriuso, Sharzad Moghadam, Elizabeth Beckett, Jane Rogan, Alison Backen, Catherine Billington, Mairéad G McNamara, Richard A Hubner, Angela Cramer and Juan W Valle

PLOS ONE, 2018, vol. 13, issue 10, 1-19

Abstract: Introduction: Expression of human epidermal growth factor receptor (HER)2 and HER3 have been investigated in small BTC studies using variable scoring systems. Methods: HER2 and HER3 overexpression/amplification were explored following internationally agreed guidelines using immunohistochemistry (IHC) and fluorescent in-situ hybridisation (FISH), respectively. Logistic regression and survival analysis (Kaplan Meier, Log rank test and Cox Regression) were used for statistical analysis. Results: Sixty-seven eligible patients with Stage I/II (31.3%) or III/IV (68.7%) disease at diagnosis were included. Membrane HER2 overexpression/amplification was identified in 1 patient (1%). HER3 overexpression was predominantly cytoplasmic; the rate of overexpression/amplification of HER3 in membrane and cytoplasm was 16% [ampullary cancer (AMP) (1/13; 8%), gallbladder cancer (GBC) (1/10; 10%), intra-hepatic cholangiocarcinoma (ICC) (6/26; 23%), extra-hepatic cholangiocarcinoma (ECC) (3/18; 17%)] and 24% [AMP (1/13; 8%), GBC (1/10; 10%), ICC (10/26; 38%), ECC (4/18; 22%)], respectively. Conclusions: A significant subset of patients with BTC expressed HER3. Inhibition of HER3 warrants further investigation. A better understanding of the downstream effects of HER3 in BTC requires further mechanistic investigations to identify new biomarkers and improve patient selection for future clinical trials.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0206007

DOI: 10.1371/journal.pone.0206007

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