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Reduced ß-Catenin Expression in the Cytoplasm of Advanced-Stage Superficial Spreading Malignant Melanoma¹

Department of Tumor Biology, Institute for Cancer Research [G. M. M., Ø. F.] and Department of Pathology [R. H., J. M. N., V. A. F.], The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway

Purpose: The purpose of the present work was to analyze the expression of ß-catenin in a panel of superficial and nodular spreading primary and metastatic melanomas, and to correlate the level of immunohistochemical staining to clinicopathological parameters.

Experimental Design: Expression of ß-catenin was examined by immunohistochemistry in 106 superficial and 58 nodular spreading primary melanomas, as well as in 66 metastatic lesions.

Results: Membrane-associated staining was detected in nearly all of the cases, and no association to clinical parameters could be revealed. When cytoplasmic localization of the protein was recorded, a significant higher fraction of the superficial than the nodular spreading primary lesions expressed the protein in the majority of the cells (P < 0.0001). Interestingly, metastatic lesions from superficial melanomas demonstrated down-regulated expression of the protein, and in agreement with this a significant inverse correlation between protein expression and the vertical thickness of the primary lesion was detected (P = 0.012). Furthermore, a significant correlation between cytoplasmic localization and disease-free survival (P = 0.0006) was revealed, but ß-catenin did not have any significant impact on overall survival for this group of patients (P = 0.0824). No association was detected between ß-catenin expression and clinicopathological parameters in the nodular subgroup of melanomas, indicating that the protein may play different roles in the malignant progression of the two main types of melanomas.

Conclusion: In summary, we hypothesize that cytoplasmic ß-catenin has a protective role in early melanoma development.

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