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 language | English |
|---|---|
| Article number | e0206007 |
| Journal | PLoS One |
| Volume | 13 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2018 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - The HR3 pathway as a potential target for inhibition in patients with biliary tract cancers
AU - Lamarca, Angela
AU - Galdy, Salvatore
AU - Barriuso, Jorge
AU - Moghadam, Sharzad
AU - Beckett, Elizabeth
AU - Rogan, Jane
AU - Backen, Alison
AU - Billington, Catherine
AU - McNamara, Mairéad G.
AU - Hubner, Richard A.
AU - Cramer, Angela
AU - Valle, Juan W.
PY - 2018/10/1
Y1 - 2018/10/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055072549&partnerID=8YFLogxK
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U2 - 10.1371/journal.pone.0206007
DO - 10.1371/journal.pone.0206007
M3 - Article
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e0206007
ER -