Resumen de P-cadherin expression predicts clinical outcome in oral squamous cell carcinomas
Lorenzo Lo Muzio, Giuseppe Pannone, Michele D. Mignogna, Stefania Staibano, M.A. Mariggiò, Corrado Rubini, M. Procaccini, M. Dolci, Pantaleo Bufo, Gaetano De Rosa, A. Piattelli
P-cadherin, a transmembrane molecule similar to E-cadherin involved in the cell-cell adhesion, and catenins form complexes between its cytoplasmic domain and the cytoskeleton. Five cell lines, 108 specimens of oral squamous cell carcinomas (OSCC), 9 metastasis and 10 of normal oral mucosa were examined to evaluate P-cadherin expression and cellular localization by immunohistochemistry and western-blotting. In normal oral mucosa there was a membranous expression only in basal and parabasal layers. 91 cases (84%) showed membranous/cytoplasmic positivity, whereas 17 cases (16%) were negative. In particular, while well-differentiated carcinomas showed P-cadherin upregulation, the protein was homogeneously hypo- or unexpressed in low-differentiated carcinomas. There was a statistically significant correlation between P-cadherin expression and tumour grading: G3 tumours had a lower score than G1-G2 tumours (P<0.05). When analysed for prognostic significance, patients with no P-cadherin expression (score 0) had poorer overall and diseases-free survival rates than the P-cadherin-expressing group (score 1) (P=0.0463 and P=0.0471, respectively). Western blotting analysis of cell lines and tissue samples confirmed immunohistochemical findings. When cell staining pattern of positive cases was examined, 52 cases showed a prevalent membranous pattern, while 39 had a prevalent cytoplasmic pattern. Cases with prevalent cytoplasmic staining showed high rates of lymph node metastases (P>0.05), and regional relapse (P <0.05) and poorer survival rates than the group with prevalent membranous expression (P<0.0001). An absent P-cadherin expression could constitute a hallmark of aggressive biological behaviour in oral squamous cell carcinoma.
