title: The Potential Prognostic Value of Connexin 43 Expression in Head and Neck Squamous Cell Carcinomas.
abstract: 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, aurora A, geminin, and p21 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/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 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 protein levels may have a significant negative impact on HNSCC prognosis.
authors.affiliation: *Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University †MTA-SE Pathobiochemistry Research Group ‡Faculty of Medicine §1st Department of Pathology and Experimental Cancer Research, Semmelweis University ∥MTA-SE Tumor Progression Research Group, Budapest, Hungary.
authors.forename: Kornél
authors.initials: K
authors.lastname: Dános
authors.forename: Diána
authors.initials: D
authors.lastname: Brauswetter
authors.forename: Ede
authors.initials: E
authors.lastname: Birtalan
authors.forename: Anna
authors.initials: A
authors.lastname: Pató
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bencsik
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenács
authors.forename: István
authors.initials: I
authors.lastname: Peták
authors.forename: László
authors.initials: L
authors.lastname: Tamás
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018031:Connexin 43; D020741:rho GTP-Binding Proteins