Oncotarget

Research Papers:

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

Heike Loeser, Simon Schallenberg, Moritz von Winterfeld, Lars Tharun, Hakan Alakus, Arnulf Hölscher, Elfriede Bollschweiler, Reinhard Buettner, Thomas Zander and Alexander Quaas _

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Oncotarget. 2017; 8:115179-115189. https://doi.org/10.18632/oncotarget.23112

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Abstract

Heike Loeser1,*,**, Simon Schallenberg1,*,**, Moritz von Winterfeld1, Lars Tharun1, Hakan Alakus3,*, Arnulf Hölscher4, Elfriede Bollschweiler3, Reinhard Buettner1, Thomas Zander2,*,** and Alexander Quaas1,*,**

1Institute of Pathology, University of Cologne, Cologne, Germany

2Department I of Internal Medicine, Center for Integrated Oncology (CIO), University of Cologne, Cologne, Germany

3Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany

4Department 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: [email protected]

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).


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