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
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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.
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(3):1382-1393.
Slotta-Huspenina, Julia; Becker, Karl-Friedrich; Feith, Marcus; Walch, Axel; Langer, Rupert. 2014. "Heat Shock Protein 90 (HSP90) and Her2 in Adenocarcinomas of the Esophagus." Cancers 6, no. 3: 1382-1393.