Connexine als potenzielle Biomarker für den Progress oraler Plattenepithelkarzinome: Analyse der Expressionsmuster von Connexin 26, 43 und 45 und ihres Einflusses auf das Überleben

Connexins as potential biomarkers for the progression of oral squamous cell carcinoma: analysis of the expression pattern of connexin 26, 43 and 45 and their influence on survival

by Phillipp Brockmeyer
Doctoral thesis
Date of Examination:2014-07-02
Date of issue:2014-06-16
Advisor:PD Dr. Bernhard Hemmerlein
Referee:PD Dr. Bernhard Hemmerlein
Referee:Prof. Dr. Ralph Rödel
Persistent Address: http://dx.doi.org/10.53846/goediss-4545

 

 

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Abstract

English

The aim of the present study was to evaluate the expression and localization of connexin (Cx) 26, -43 and -45 in a group of 35 patients with primary oral squamous cell carcinoma (OSCC) with the objective of making a more accurate disease prognosis. We analysed the expression of connexins in tissue samples of primary OSCC, matching oral mucosa free of dysplasia, and it’s associated lymph node metastases (LNM) by semiquantitative immunohistochemistry of membrane, cytoplasmic and nuclear connexin expression. The level of expression was correlated with the overall survival time (OS). Cx43 was overexpressed in tumour cells compared to epithelia in dysplasia-free mucosa. High membrane expression of Cx43 on tumour cells was the only statistically significant and independent prognostic factor of short OS (p=0.0088). Membrane expression of Cx43 in matching dysplasia-free mucosa acted similarly, but did not reach statistical significance (p=0.059). No correlation was found between the Cx26, Cx45 expression and OS. We conclude that Cx43 expression in dysplasia-free mucosa may indicate a very early stage of tumour promotion. Although overexpression of Cx43 is found in invasive tumours we only found membrane Cx43 expression to correlate with OS. This observation suggests that cytoplasmic Cx43 serves as storage and only membrane translocation may promote the formation of gap junctions and gap junctional intercellular communication (GJIC) with prognostic relevance.
Keywords: gap junctional intercellular communication; oral squamous cell carcinoma; connexin 26; connexin 43; connexin 45; prognosis
 
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