Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays.
OBJECTIVE
To investigate whether protein expression or cellular localisation of P-cadherin is associated with clinicopathological characteristics in benign and malignant melanocytic skin tumours.


METHODS
P-cadherin expression and the Ki-67 labelling index were analysed immunohistochemically by using tissue microarrays (TMAs). Membranous and cytoplasmic expression was scored semiquantitatively (0 to 2+).


RESULTS
P-cadherin protein expression of any intensity (1+ to 2+) was detected in the membrane in 41.5% (132/318) and in the cytoplasm in 64.2% (204/318) of patients. In general, P-cadherin expression was significantly reduced in malignant melanomas (p<0.001) and melanoma metastases (p<0.001), compared with benign nevi. Additionally, loss of membranous P-cadherin was associated with Clark level (p = 0.011) and tumour thickness (p<0.001). Interestingly, a significantly lower P-cadherin expression was shown by dermal nevi than by compound and junctional nevi (p = 0.005; p = 0.025). In primary melanomas, a Ki-67 labelling index <5% was not associated with P-cadherin protein expression, suggesting that loss of P-cadherin expression was not associated with proliferation. None of the other clinical and histological factors analysed was significantly related to P-cadherin expression. Low cytoplasmic P-cadherin expression was associated with tumour recurrence (p = 0.03) in all the patients who were analysed. After testing various multivariate Cox regression models, loss of cytoplasmic P-cadherin expression remained a highly significant adverse risk factor for tumour recurrence in patients with tumours <2 mm.


CONCLUSIONS
Loss of cytoplasmic P-cadherin expression is common in advanced melanomas and can be a prognostic marker of progression in patients with melanoma, most useful in patients with primary tumours <2 mm in thickness.
Institute of Pathology, University of Regensburg, Germany.
R
R
Bauer
P J
PJ
Wild
S
S
Meyer
F
F
Bataille
A
A
Pauer
M
M
Klinkhammer-Schalke
F
F
Hofstaedter
A K
AK
Bosserhoff
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D009508:Nevus, Pigmented / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D012008:Recurrence; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D015820:Cadherins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins