title: Heat Shock Protein 90 (HSP90) and Her2 in Adenocarcinomas of the Esophagus.
abstract: Her2 overexpression and amplification can be found in a significant subset of esophageal adenocarcinomas. The activity of Her2 has been shown to be modulated by molecular chaperones such as HSP90. We analyzed expression/amplification data for HSP90 and Her2 on 127 primary resected esophageal adenocarcinomas in order to evaluate a possible relationship between these two molecules. HSP90 expression determined by immunohistochemistry was observed in various levels. Thirty nine (39) tumors (30.7%) were classified as Her2-positive according to their immunoreactivity and amplification status. There was a significant correlation between HSP90 expression and Her2-status (p = 0.008). This could also be demonstrated by quantitative protein expression analysis with reverse phase protein arrays (r = 0.9; p < 0.001). Her2-status was associated withpT-category (p = 0.041), lymph node metastases (p = 0.049) and tumor differentiation (p = 0.036) with a higher percentage of cases with negative Her2 status in lower tumor stagesA negative Her2-status was also associated with better survival in univariate and multivariate analysis (p = 0.001 and p = 0.014). For HSP90, no associations between clinical and pathological parameters were found. The observed association between HSP90 expression and Her2 suggests a co-regulation of these molecules in at least a subset of esophageal adenocarcinomas. Anti-HSP90 drugs, which recently have been introduced in cancer treatment, may also be an option for these tumors by targeting HSP90 alone or in combination with Her2.
authors: Institute of Pathology, Technische Universität München, München 81765, Germany. slotta-huspenina@lrz.tum.de.
authors: Julia
authors: J
authors: Slotta-Huspenina
authors: Institute of Pathology, Technische Universität München, München 81765, Germany. kfbecker@lrz.tum.de.
authors: Karl-Friedrich
authors: KF
authors: Becker
authors: Department of Surgery, Klinikum Rechts der Isar der Technischen Universität München, München 81622, Germany. marcus.feith@tum.de.
authors: Marcus
authors: M
authors: Feith
authors: Institute of Pathology, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg 85764, Germany. axel.walch@helmholtz-muenchen.de.
authors: Axel
authors: A
authors: Walch
authors: Institute of Pathology, University of Bern, Bern 3010, Switzerland. rupert.langer@pathology.unibe.ch.
authors: Rupert
authors: R
authors: Langer