Abstract
BackgroundEsophageal 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.ResultsThere 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.DiscussionOur 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 Methods280 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).
Highlights
Esophageal cancer is the eighth most common malignant tumor diagnosed in the world
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
We found an excellent correlation of mRNA expression and protein levels measured by immunohistochemistry for TUBB3 – tumors exhibited high protein levels showed elevated mRNA levels and vice versa
Summary
Esophageal cancer is the eighth most common malignant tumor diagnosed in the world. squamous cell cancer is the most frequent tumor type, esophageal adenocarcinomas show an increasing incidence in the Western world [1]. It is thought that the microtubulus-TUBB3 isotype is responsible for generating the highly dynamic microtubules required for neurite formation and motility in neuronal tissues [4] It was found overexpressed in several solid tumors, including non-small cell lung cancer [5], ovarian cancer [6, 7], urothelial carcinoma of the bladder [8] and head and neck squamous cell carcinoma [9], suggesting a significant role in cancer development [6]. Overexpression of βIII-tubulin was shown to be related to reduced efficiency of taxane-based targeting anticancer drugs in several cancer types [11]. In a study of gastric cancer, pre-treatment immunohistochemical evaluation of βIII-tubulin was predictive for taxane-based chemotherapy in advanced tumor stages [12]. It was shown that overexpression of TUBB3 could be related to reduced efficiency of taxane-based targeting anticancer drugs in several cancer types
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