P-cadherin expression predicts clinical outcome in oral squamous cell carcinomas.
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.
Lo Muzio
L
L
Institute of Dental Sciences, University of Ancona, Ancona, Italy. lomuziol@tin.it
Pannone
G
G
Mignogna
M D
MD
Staibano
S
S
Mariggiò
M A
MA
Rubini
C
C
Procaccini
M
M
Dolci
M
M
Bufo
P
P
De Rosa
G
G
Piattelli
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D016022:Case-Control Studies; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
D015820:Cadherins