HER2/neu (ERBB2) expression and gene amplification correlates with better survival in esophageal adenocarcinoma

Patrick Sven Plum†,
Florian Gebauer†,
Max Krämer,
Hakan Alakus,
Felix Berlth,
Seung-Hun Chon,
Lars Schiffmann,
Thomas Zander,
Reinhard Büttner,
Arnulf Heinrich Hölscher,
Christiane Josephine Bruns,
Alexander Quaas† and
Heike Loeser†Email author

†Contributed equally

BMC Cancer201919:38

https://doi.org/10.1186/s12885-018-5242-4

Received: 28 June 2018
Accepted: 21 December 2018
Published: 8 January 2019

Open Peer Review reports

Abstract

Background

HER2 (ERBB2 or HER2/neu) is a tyrosine-kinase increasing cell proliferation. Overexpression/amplification of HER2 is correlated with worse prognosis in solid malignancies. Consequently, HER2 targeting is established in breast and upper gastrointestinal tract cancer. There are conflicting data concerning the impact of HER2 overexpression on esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the esophagus/gastroesophageal junction and the stomach. The aim of this study was to analyze the expression/amplification of HER2 in EAC in correlation to clinicopathological data to verify its prognostic impact.

Methods

We analyzed 428 EAC patients that underwent transthoracic thoraco-abdominal esophagectomy between 1997 and 2014. We performed HER2 immunohistochemistry (IHC) according to the guidelines and fluorescence-in-situ-hybridization (FISH) for IHC score2+, using tissue micro arrays (TMA) with up to eight biopsies from the surface and infiltration area of a single tumor for evaluating HER2-heterogeneity and single-spot TMA. The HER2-status was correlated with clinicopathological data.

Results

HER2-positivity was found in up to 14.9% in our cohort (IHC score 3+ or IHC score 2+ with gene amplification) and demonstrated a significantly better overall survival (OS) in correlation to HER2-negative tumors (median OS 70.1 vs. 24.6 months, p = 0.006). HER2-overexpression was more frequently seen in lower tumor stages (pT1/pT2, p = 0.038), in the absence of lymphatic metastases (pN0/pN+, p = 0.020), and was significantly associated with better histological grading (G1/G2) (p = 0.041).

Conclusion

We demonstrated a positive prognostic impact of HER2 overexpression in a large cohort of EAC, contrary to other solid malignancies including gastric cancer and breast cancer, but consistent to the results of a large study on EAC from 2012.