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Background Targeting Her2 is highly established in cancers of the upper gastrointestinal tract, since clinical studies showed a survival benefit in Her2-positive gastric cancer. To date there is conflicting data concerning the impact of Her2 expression and gene amplification in esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the esophagus, gastroesophageal junction and stomach. The aim of this study was to analyze the expression and gene amplification of Her2 in EAC in correlation to clinical and pathological data to verify the prognostic impact. Methods We analyzed 506 patients with esophageal adenocarcinomas that underwent thoraco-abdominal esophagectomy between 1997 and 2013 using a tissue micro array (TMA) for the expression of Her2 by immunohistochemistry (IHC) according to the guidelines. Fluorescence-in-situ-hybridization (FISH) was performed for IHC score 2. The Her2-status was correlated with clinical and pathological data. Results Her2-positivity was found in 11.7% (n = 59) of all EAC (IHC score 3 + or IHC score 2 + with amplification) and demonstrated a significant better overall-survival (OS) in correlation to Her2-negative tumors (median OS 55.0 vs. 22.7 months, P  < 0.0001) (Figure below). Overexpression of Her2 was associated with lower tumor stages (pT1/pT2, P  = 0.038), absence of lymph node metastases (pN0/pN + , P  = 0.030) and was significantly associated with tubular and/or papillary tumor growth pattern (P  = 0.029). View large Download slide View large Download slide Conclusion We demonstrated a positive prognostic impact of Her2 expression and gene amplification in a large cohort of EAC, contrary to other solid malignancies including gastric cancer, but according to a large study of EAC from 2012. Her2-positive tumors significantly have a tubular and/or papillary tumor growth pattern, indicating a marker of differentiation in EAC. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Immunotherapy has grown to a rapidly advancing sphere of research on modern strategies for treatment of cancer. A well-known way of immunomodulation is the principle of immune checkpoints leading to a down-regulated immune response in tumor microenvironment. Recently, beside the PD1/PD-L1 pathway, several immunecheckpoint pathways have been found. However, almost nothing is known about the expression and the correlation as prognostic factor in esophageal adenocarcinoma. Methods Two tissue micro arrays (TMA) were construced, a multi-spot TMA with up to 8 spots from different tumor areas of 165 patients and a valdiation single-spot TMA of 620 patients with EAC. Immunehistochemistry analysis were performed for LAG3, Tim3, IDO, VISTA, MHC1, MHC2, CD3, CD8, CD20 and CD38 and correlated with clinico-pathological and survival data. Data were additionally correlated with molecular data like TP53 mutational and HER2-neu status. Results LAG3 was detectable in 13.5% of all tumors, VISTA in 40.2%, IDO in 57.9%, Tim3 in 36.3%. There was only minor intratumoral heterogeneity between the luminal and infiltration area of the tumor for all analyzed immunecheckpoints. LAG3 and VISTA expression on tumor infiltrating T-cells (TIL) was associated with superior overall-survival compared to LAG3 and VISTA negative tumors. In pT1/2 tumors, VISTA was found as excellent independent prognosticator identifiying long-term surivors in case of VISTA expression. High amount of CD3 positive TILs was also associated with a better OS than CD3 poor tumors. Conclusion We conducted an extensive analysis of the immunecheckpoint status and presecnce of TILs in EAC. To the best of our knowledge, this is the first report in a large patients cohort correlating the expression of LAG3, Tim3, IDO and VISTA in EAC. The prognostic impact of LAG3 and VISTA expression suggests potential promising targets for novel immune checkpoint inhibition therapies beyond the PD1/PD-L1 inhibition as it is already established in head and neck cancer and NSCLC. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]