Prognostic relevance of P-cadherin expression in melanocytic skin tumours analyzed by high-throughput tissue microarrays

¹ Institute of Pathology, University of Regensburg, Germany
² Dept. of Dermatology, University of Regensburg, Germany
³ University of Regensburg, Germany
⁴ Central Tumor Registry, Regensburg,, Germany
⁵ Central Tumor Registry, Regensburg, Germany
⁶ Insitute of Pathology, University of Regensburg, Germany

^* To whom correspondence should be addressed. E-mail: anja.bosserhoff{at}klinik.uni-regensburg.de.

Accepted 1 December 2005

	Abstract

Purpose: To investigate whether protein expression or cellular localization of P-cadherin is associated with clinico-pathologic characteristics in benign and malignant melanocytic skin tumors.

Experimental Design: Tissue microarrays (TMAs) were used to analyze P-cadherin expression and the Ki-67 labeling index immunohistochemically. Membranous and cytoplasmic expression was scored semi quantitatively (0-2+).

Results: P-cadherin protein expression of any intensity (1+-2+) was detected in the membrane in 41.5% (132/318) and in the cytoplasm in 64.2% (204/318) of informative cases. In general, P-cadherin expression was significantly reduced in malignant melanomas (P<0.001) and melanoma metastases (P<0.001), compared to benign nevi. Additionally, loss of membranous P-cadherin was associated with Clark level (P=0.011) and tumor thickness (P<0.001). Interestingly, also dermal nevi demonstrated a significantly lower P-cadherin expression compared to compound and junctional nevi (P=0.005; P=0.025). In primary melanomas, Ki-67 labeling index <5% was not associated with P-cadherin protein expression suggesting that loss of P-cadherin expression is not associated with proliferation. None of the other clinical and histological factors analyzed was significantly related to P-cadherin expression. If all patients were analyzed, low cytoplasmic P-cadherin expression was associated with tumor recurrence (P=0.03). Testing various multivariate Cox regression models, loss of cytoplasmic P-cadherin expression remained a highly significant adverse risk factor for tumor recurrence in patients with tumors <2mm.

Conclusions: Loss of cytoplasmic P-cadherin expression is frequent in advanced melanomas and could be a prognostic marker of progression in melanoma patients; most useful in patients with primary tumors less than 2mm in thickness.

Key Words: cadherin, immunohistochemistry, malignant melanoma, prognosis, tissue array

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