High protein and mRNA expression levels of TUBB3 (class III ß-tubulin) are associated with aggressive tumor features in esophageal adenocarcinomas

// Heike Loeser 1, *, ** , Simon Schallenberg 1, *, ** , Moritz von Winterfeld 1 , Lars Tharun 1 , Hakan Alakus 3, * , Arnulf Holscher 4 , Elfriede Bollschweiler 3 , Reinhard Buettner 1 , Thomas Zander 2, *, ** and Alexander Quaas 1, *, ** 1 Institute of Pathology, University of Cologne, Cologne, Germany 2 Department I of Internal Medicine, Center for Integrated Oncology (CIO), University of Cologne, Cologne, Germany 3 Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany 4 Department of Thorax and Oesophageal Surgery, Agaplesion Markus Krankenhaus, Frankfurt/Main, Germany * Gastrointestinal Cancer Group Cologne (GCGC) ** These authors have contributed equally to this work Correspondence to: Alexander Quaas, email: alexander.quaas@uk-koeln.de Keywords: esophageal adenocarcinoma; TUBB3; RNA-in-situ-hybridization; immunohistochemistry Received: May 10, 2017     Accepted: November 20, 2017     Published: December 11, 2017 ABSTRACT Background: Esophageal adenocarcinomas show an increasing incidence in the Western world and their overall survival remains low. Microtubules are multifunctional cytoskeletal proteins involved in crucial cellular roles, including maintenance of cell shape, intracellular transport, meiosis, and mitosis. Microtubulus-TUBB3 was found overexpressed in several carcinomas suggesting a significant role in cancer development. High levels of TUBB3 expression were also described to be associated with poor clinical outcome in various cancers. It was shown that overexpression of TUBB3 could be related to reduced efficiency of taxane-based targeting anticancer drugs in several cancer types. Results: There is a statistically significant association between high TUBB3 protein and TUBB3 mRNA expression and shortened survival (p<0,0001). Prognostic impact of TUBB3 expression is seen in patients with and without multimodal treatment. Multivariate analysis revealed a strong TUBB3 expression to be an independent prognosis factor. Validation of protein expression by mRNA in situ hybridization underlines the credibility of the immunohistochemical results. Discussion: Our study emphasized the significant importance of TUBB3 in esophageal adenocarcinoma. TUBB3 serves as an independent prognostic marker and may be a valuable biomarker for routine application in esophageal adenocarcinoma especially to address the need for adjuvant treatment in individuals following neoadjuvant therapy and surgery. Future prospective studies are needed which include the results of TUBB3 in preoperative biopsy material to proof the prognostic impact of TUBB3. Materials and Methods: 280 esophageal adenocarcinomas that underwent primary surgical resection or resection after neoadjuvant therapy were analyzed by mRNA-in-situ-hybridization (RNAscope ® ) and by immunohistochemistry (TUBB3 rabbit monoclonal antibody; Epitomics).