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Cancers 2014, 6(3), 1382-1393; doi:10.3390/cancers6031382
Article

Heat Shock Protein 90 (HSP90) and Her2 in Adenocarcinomas of the Esophagus

1
,
1
,
2
,
3
 and
4,*
1 Institute of Pathology, Technische Universität München, München 81765, Germany 2 Department of Surgery, Klinikum Rechts der Isar der Technischen Universität München, München 81622, Germany 3 Institute of Pathology, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg 85764, Germany 4 Institute of Pathology, University of Bern, Bern 3010, Switzerland
* Author to whom correspondence should be addressed.
Received: 16 January 2014 / Revised: 25 April 2014 / Accepted: 16 June 2014 / Published: 27 June 2014
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)
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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.
Keywords: HSP90; Her2; esophageal adenocarcinoma; immunohistochemistry; RPPA; in situ hybridization HSP90; Her2; esophageal adenocarcinoma; immunohistochemistry; RPPA; in situ hybridization
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Slotta-Huspenina, J.; Becker, K.-F.; Feith, M.; Walch, A.; Langer, R. Heat Shock Protein 90 (HSP90) and Her2 in Adenocarcinomas of the Esophagus. Cancers 2014, 6, 1382-1393.

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