Membrane connexin 43 acts as an independent prognostic marker in oral squamous cell carcinoma

Int J Oncol. 2014 Jul;45(1):273-81. doi: 10.3892/ijo.2014.2394. Epub 2014 Apr 23.


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 its associated lymph node metastases (LNM) by semi-quantitative immunohistochemistry of membrane, cytoplasmic and nuclear connexin expression. The levels of expression were 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.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Membrane / metabolism
  • Connexin 26
  • Connexin 43 / metabolism*
  • Connexins / metabolism*
  • Female
  • Humans
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Mucous Membrane / metabolism
  • Survival Analysis
  • Up-Regulation


  • Biomarkers, Tumor
  • Connexin 43
  • Connexins
  • GJB2 protein, human
  • connexin 45
  • Connexin 26