Background: HER2 (ERBB2 or HER2/neu) is a tyrosine-kinase increasing cell proliferation. Overexpression/\namplification of HER2 is correlated with worse prognosis in solid malignancies. Consequently, HER2 targeting is\nestablished in breast and upper gastrointestinal tract cancer. There are conflicting data concerning the impact of\nHER2 overexpression on esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the\nesophagus/gastroesophageal junction and the stomach. The aim of this study was to analyze the expression/\namplification of HER2 in EAC in correlation to clinicopathological data to verify its prognostic impact.\nMethods: We analyzed 428 EAC patients that underwent transthoracic thoraco-abdominal esophagectomy\nbetween 1997 and 2014. We performed HER2 immunohistochemistry (IHC) according to the guidelines and\nfluorescence-in-situ-hybridization (FISH) for IHC score2+, using tissue micro arrays (TMA) with up to eight biopsies\nfrom the surface and infiltration area of a single tumor for evaluating HER2-heterogeneity and single-spot TMA. The\nHER2-status was correlated with clinicopathological data.\nResults: HER2-positivity was found in up to 14.9% in our cohort (IHC score 3+ or IHC score 2+ with gene\namplification) and demonstrated a significantly better overall survival (OS) in correlation to HER2-negative tumors\n(median OS 70.1 vs. 24.6 months, p = 0.006). HER2-overexpression was more frequently seen in lower tumor stages\n(pT1/pT2, p = 0.038), in the absence of lymphatic metastases (pN0/pN+, p = 0.020), and was significantly associated\nwith better histological grading (G1/G2) (p = 0.041).\nConclusion: We demonstrated a positive prognostic impact of HER2 overexpression in a large cohort of EAC,\ncontrary to other solid malignancies including gastric cancer and breast cancer, but consistent to the results of a\nlarge study on EAC from 2012.
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