Abstract
BackgroundHER2 (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.MethodsWe 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.ResultsHER2-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).ConclusionWe 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.
Highlights
human epidermal growth factor receptor 2 (HER2) (ERBB2 or HER2/neu) is a tyrosine-kinase increasing cell proliferation
Significant efforts have been made in this field, resulting in the description of a large variety of different putative markers, but so far, only one of them has made its way into the guidelines for targeted therapy for patients with advanced gastroesophageal adenocarcinoma, namely the human epidermal growth factor receptor 2 (HER2) [7]
In patients with HER2-positive advanced gastric or esophagogastric junction adenocarcinoma, the use of trastuzumab in combination with chemotherapy is a standard therapy concept and has a positive prognostic effect compared to chemotherapeutic treatment alone [14]
Summary
HER2 (ERBB2 or HER2/neu) is a tyrosine-kinase increasing cell proliferation. Overexpression/ amplification of HER2 is correlated with worse prognosis in solid malignancies. 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. Significant efforts have been made in this field, resulting in the description of a large variety of different putative markers, but so far, only one of them has made its way into the guidelines for targeted therapy for patients with advanced gastroesophageal adenocarcinoma, namely the human epidermal growth factor receptor 2 (HER2) [7]. In patients with HER2-positive advanced gastric or esophagogastric junction adenocarcinoma, the use of trastuzumab in combination with chemotherapy is a standard therapy concept and has a positive prognostic effect compared to chemotherapeutic treatment alone [14]. According to the current literature, the rate of HER2 positivity in EAC varies, ranging from 15 to 29% [19,20,21,22,23,24]
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