title: Dysadherin expression in head and neck squamous cell carcinoma: association with lymphangiogenesis and prognostic significance.
abstract: Dysadherin is a recently characterized cancer-associated cell membrane glycoprotein that has a crucial role to cell-cell adhesiveness. The aim of this study was to examine dysadherin expression in head and neck squamous cell carcinoma (HNSCC). A total of 108 tissue specimens of patients with HNSCC were examined using immunostaining for dysadherin, E-cadherin, and the specific lymphatic endothelium marker D2-40. We quantified dysadherin and E-cadherin expression, assessed intratumoral (ILD) and peritumoral lymphatic density (PLD), and examined the possible associations of all the above parameters with clinicopathologic features and outcome. Finally, we used double staining with dysadherin and D2-40 to examine the expression pattern of dysadherin simultaneously with the lymphovasculature environment of HNSCC. High dysadherin expression was correlated with higher clinical stage (chi2, P = 0.01), with the presence of lymph node metastasis at the time of diagnosis (chi2, P = 0.02), and with increased ILD (chi2, P = 0.001). We observed an impressive reverse association between increased dysadherin expression and decreased E-cadherin expression (chi2, P < 0.001). Surprisingly, dysadherin-positive cancer cells usually gathered around areas of high intratumoral lymphatic vessel concentration, surrounding and invading small intratumoral lymphatics. Higher clinical stage and increased dysadherin expression were found to be the only significant independent prognostic factors for overall survival (hazard ratio, 3.94; 95% confidence interval, 1.09-14.27 for clinical stage; hazard ratio, 3.92; 95% confidence interval, 1.46-10.51 for dysadherin). The loss of intercellular adhesiveness and increased dysadherin expression seems to be related to lymphangiogenesis in HNSCC, but this should be confirmed by additional studies. Dysadherin expression might be a promising prognostic marker for separation of patients at higher risk.
authors.affiliation: Department of Pathology, University of Ioannina, Medical School, Ioannina, Greece. md03791@cc.uoi.gr
authors.forename: Panayiotis A
authors.initials: PA
authors.lastname: Kyzas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stefanou
authors.forename: Anna
authors.initials: A
authors.lastname: Batistatou
authors.forename: Niki J
authors.initials: NJ
authors.lastname: Agnantis
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Charalabopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D004729:Endothelium, Lymphatic / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels; D008207:Lymphatic Metastasis / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D015820:Cadherins; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C500987:monoclonal antibody D2-40