Bcl-2 expression in human melanocytes and melanocytic tumors.

During an immunohistochemical study of the distribution of the Bcl-2 proto-oncogene product in frozen sections of normal human skin, a hitherto unrecognized strong reactivity with melanocytes was observed. This prompted us to study Bcl-2 expression in a variety of pigment lesions. In nevocellular nevi, immunoreactivity gradually diminished or even disappeared toward the deeper dermal component. In malignant melanomas of all stages and histological subtypes, the neoplastic cells expressed Bcl-2 oncoprotein, the most intense positivity being restricted to cells in the radial growth phase. Cutaneous and lymph node metastases of malignant melanomas were negative or showed only weak and focal reactivity. The specificity of the staining was confirmed by Western blotting of tissue lysates. The loss of Bcl-2 expression in the deeper parts of nevi may offer an explanation for the "maturation" and final disappearance of dermal nevocellular nevi. The expression of Bcl-2 oncoprotein by malignant melanomas adds these neoplasms to a growing list of tumors expressing this oncoprotein. Bcl-2 in malignant melanoma may play a role in tumor development by sparing the cells from apoptotic death (and thereby exposing them to secondary events) or through cooperation with other oncogenes. The lack of reactivity in metastatic melanoma suggests that mechanisms other than Bcl-2 are involved in the survival and growth of metastatic melanoma cells.