Gap juctions are transmembrane communication channels known to be involved in the control of cell proliferation by mediating the exchange of ions and small molecules between cells. Gap junctions are composed of connexon hemichannels made up of 6 connexin proteins, which abnormal expression and functions have been linked to tumor progression and poorer prognosis. Here, we studied the prognostic impact of the most prevalent connexin isotype, connexin 43 (Cx43) in head and neck squamous cell carcinomas (HNSCC). Tissue microarrays made from tumor samples of 90 HNSCC patients were immunostained for Cx43 and cell cycle regulation-related biomarkers including p53, Ki67, p16 ink4, aurora A, geminin, and p21 waf1 proteins. Scoring and histopathologic evaluation were performed in digital slides. A 4-tier scoring distinguishing the percentage of positively stained tumor cells was used including score 1: <5%, score 2: 6% to 20%, score 3: 21% to 60%, and score 4: >60%. For statistics, Kaplan-Meier curves with log-rank tests, Cox-regression, and Pearson χ 2 /Fisher exact tests were used. A significant positive correlation was found between Cx43 expression and disease-specific survival of patients (P=0.004). The rate of p21 waf1 protein-positive tumor cells also proved to be a significant positive prognostic marker (P=0.014). Cx43 levels also showed a significant positive correlation with p53 expression (P=0.036). However, there was no statistical association between Cx43 levels and the rest of the markers tested neither with T, N, or M stage. In conclusion, our data suggest that reduced Cx43 expression and low p21 waf1 protein levels may have a significant negative impact on HNSCC prognosis.
|Number of pages||6|
|Journal||Applied Immunohistochemistry and Molecular Morphology|
|Publication status||Published - jan. 1 2016|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Medical Laboratory Technology