119Alfred K. Lam (ed.), Esophageal Adenocarcinoma: Methods and Protocols, Methods in Molecular Biology, vol. 1756,
https://doi.org/10.1007/978-1-4939-7734-5_11, © Springer Science+Business Media, LLC 2018
Chapter 11
Predictive Marker: HER2 in Esophageal Adenocarcinoma
Duminda Subasinghe, Nathan Acott, and M. Priyanthi Kumarasinghe
Abstract
HER2 positivity is based on the fundamental principle of amplification of the human epidermal growth
factor receptor 2 (HER2) gene resulting in overexpression of the protein products. Arising from that a
“HER2- positive cancer” is one that shows HER2 gene amplification and resultant protein expression as
demonstrated by in situ hybridization and immunohistochemistry, respectively. Testing of the HER2 sta-
tus is crucial to ensure selection of the correct patient who may benefit from target therapy for esophageal
adenocarcinoma. Accurate testing is dependent on several pre-analytical and analytical factors including
sample selection, laboratory techniques, and accurate interpretation of HER2 test results.
Key words HER2, Immunohistochemistry, In situ hybridization, Esophageal adenocarcinoma,
Pathology1 Introduction
HER2 (receptor tyrosine-protein kinases) positivity plays a critical
role in the origin and progression including metastases of many
malignancies such as breast and gastric and esophagogastric junc-
tion cancer [ 1 , 2 ]. HER2 (c-erbB2) gene, a proto-oncogene, is
located on chromosome 17q11.2-12 and encodes for HER 2 pro-
tein. HER2 overexpression is noted in 7–25% of esophageal ade-
nocarcinoma [ 3 – 7 ]. Activation of HER-2 plays a pivotal role in cell
proliferation, inhibition of apoptosis, and cancer progression,
which is mainly mediated through the Ras/Raf/mitogen-activated
protein kinase and the phosphatidylinositol-3-kinase mammalian
target of rapamycin pathway [ 8 , 9 ]. HER2 positivity and gene
amplification are known to be independently associated with poor
survival of patients with esophageal adenocarcinoma [ 10 ].
The ToGA (trastuzumab for gastric and gastresophageal junc-
tion adenocarcinoma) study showed clinically and statistically sig-
nificant benefit in response rates, median progression-free survival,
and overall survival with the addition of the anti-HER2 biological
agent, trastuzumab to standard chemotherapeutic regimens in gas-