HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

P-cadherin expression predicts clinical outcome in oral squamous cell carcinomas

L. Lo Muzio1, G. Pannone2, M.D. Mignogna2, S. Staibano3, M.A. Mariggiò4, C. Rubini5, M. Procaccini1, M. Dolci6, P. Bufo7, G. De Rosa3 and A. Piattelli6

1Institute of Dental Sciences, University of Ancona, Ancona, Italy, 2Department of Dental Sciences, University of Naples Federico II, Naples, Italy, 3Department of Biomorphological and Functional Sciences – Pathology Unit, University of Naples Federico II, Naples, Italy, 4Department of Biomedical Sciences and Human Oncology - Section of General Pathology and Experimental Oncology, University of Bari, Bari, Italy. 5Institute of Pathology, University of Ancona, Ancona, Italy, 6Department of Dental Sciences, University of Chieti, Chieti, Italy and 7Institute of Pathology, University of Foggia, Foggia, Italy

Offprint requests to: Prof. Lorenzo Lo Muzio, MD, PhD, Via Carelli 28, 71100 Foggia, Italy. Fax: +39 (0881) 685.809. e-mail: lomuziol@tin.it

Summary. 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. Histol Histopathol 19, 1089-1099 (2004)

Key words: P-cadherin, Head and neck, Oral squamous cell carcinoma

DOI: 10.14670/HH-19.1089