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Cytoplasmic β‐catenin is lacking in a subset of melanoma‐associated naevi,but is detectable in naevus‐associated melanomas: potential implications for melanoma tumorigenesis?
Authors:G De Panfilis  D Ferrari  S Santoro  R Ricci  M Lombardi  G Pedrazzi†  C Pepe  C Cortelazzi  M Santini
Institution:Section of Dermatology, Department of Surgical Sciences;, Section of Pathology, Department of Pathology and Laboratory Medicine;and Section of Physics, Department of Public Health, University of Parma, Parma, Italy
Abstract:Summary Background An excess of intracellular β‐catenin protein is triggered by various genetic alterations in melanoma cell lines, and has been suggested to play a role in melanoma tumorigenesis. Objectives To investigate the role played in vivo by β‐catenin in melanoma tumorigenesis, we compared the cytoplasmic detection of β‐catenin in benign melanocytic cells vs. malignant melanoma cells presumably generated from these benign melanocytic cells. For this purpose, melanocytic naevi occurring in association with melanoma, which were suggested to be melanoma precursors, were compared with their associated melanoma for β‐catenin cytoplasmic immunoreactivity. Methods Fifty‐seven consecutive cases of primary cutaneous melanoma were considered, and 15 of them were found to be associated with a melanocytic naevus portion. The naevus portion showed features of acquired melanocytic naevus (total 12 cases: five dysplastic, seven intradermal) or congenital growth pattern naevus (total three cases: one superficial, two deep). All specimens were immunohistochemically investigated for β‐catenin. Results Virtually all primary cutaneous melanomas, including those associated with a naevus portion, showed cytoplasmic β‐catenin positivity. However, the intradermal naevus portion was consistently cytoplasmic β‐catenin negative, while both the dysplastic and the congenital naevus portions were cytoplasmic β‐catenin positive. Conclusions β‐Catenin excess may play a role in melanoma tumorigenesis, because β‐catenin cytoplasmic reactivity was found in primary cutaneous melanoma but not in its associated intradermal naevus precursor. As, however, β‐catenin cytoplasmic reactivity was detected not only in primary cutaneous melanoma but also in its associated dysplastic/congenital naevus precursors, β‐catenin stabilization alone is not sufficient to play a decisive role for melanoma onset.
Keywords:β-catenin  melanoma-associated naevi  naevus-associated melanomas  tumorigenesis
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