The HR3 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, Juan W. Valle

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere0206007
JournalPLoS One
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

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Biliary Tract Neoplasms
biliary tract
Cholangiocarcinoma
Amplification
Gallbladder Neoplasms
liver
neoplasms
gall bladder
Liver
Membranes
Biomarkers
Epidermal Growth Factor Receptor
Logistics
Statistical methods
Survival Analysis
fluorescence in situ hybridization
Fluorescence In Situ Hybridization
Patient Selection
immunohistochemistry
clinical trials

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lamarca, A., Galdy, S., Barriuso, J., Moghadam, S., Beckett, E., Rogan, J., ... Valle, J. W. (2018). The HR3 pathway as a potential target for inhibition in patients with biliary tract cancers. PLoS One, 13(10), [e0206007]. https://doi.org/10.1371/journal.pone.0206007

The HR3 pathway as a potential target for inhibition in patients with biliary tract cancers. / Lamarca, Angela; Galdy, Salvatore; Barriuso, Jorge; Moghadam, Sharzad; Beckett, Elizabeth; Rogan, Jane; Backen, Alison; Billington, Catherine; McNamara, Mairéad G.; Hubner, Richard A.; Cramer, Angela; Valle, Juan W.

In: PLoS One, Vol. 13, No. 10, e0206007, 01.10.2018.

Research output: Contribution to journalArticle

Lamarca, A, Galdy, S, Barriuso, J, Moghadam, S, Beckett, E, Rogan, J, Backen, A, Billington, C, McNamara, MG, Hubner, RA, Cramer, A & Valle, JW 2018, 'The HR3 pathway as a potential target for inhibition in patients with biliary tract cancers', PLoS One, vol. 13, no. 10, e0206007. https://doi.org/10.1371/journal.pone.0206007
Lamarca A, Galdy S, Barriuso J, Moghadam S, Beckett E, Rogan J et al. The HR3 pathway as a potential target for inhibition in patients with biliary tract cancers. PLoS One. 2018 Oct 1;13(10). e0206007. https://doi.org/10.1371/journal.pone.0206007
Lamarca, Angela ; Galdy, Salvatore ; Barriuso, Jorge ; Moghadam, Sharzad ; Beckett, Elizabeth ; Rogan, Jane ; Backen, Alison ; Billington, Catherine ; McNamara, Mairéad G. ; Hubner, Richard A. ; Cramer, Angela ; Valle, Juan W. / The HR3 pathway as a potential target for inhibition in patients with biliary tract cancers. In: PLoS One. 2018 ; Vol. 13, No. 10.
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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.",
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N2 - 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.

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