MELANOMA-ASSOCIATED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS

Melanocytic neoplasia is characterized by the aberrant overproduction of multiple cytokines in vitro. However, it is largely unknown how cyt okine expression relates to melanoma progression in vivo. Transforming growth factor beta (TGF-beta) is a multifunctional cytokine commonly produced by cultured melanoma cells. The in situ expression of all thr ee TGF-beta isoforms (TGF-beta 1, -2, and -3) was determined immunohis tochemically in melanocytes and in 51 melanocytic lesions using isofor m-specific antibodies. Significant linear trends of expression were ob served from melanocytes through nevi and primary and metastatic melano mas for all three isoforms. TGF-beta 1 was expressed by some melanocyt es and almost uniformly by nevi and melanomas. TGF-beta 2 and -3 were not expressed in normal melanocytes but were expressed in nevi and ear ly and advanced primary (radial and vertical growth phase) and metasta tic melanomas in a tumor-progression-related manner. TGF-beta 2 suns h eterogeneously expressed It advanced primary and metastatic melanomas, whereas TGF-beta 3 was uniformly and highly expressed in these lesion s. Thus, expression of TGF-beta isoforms in melanocytes and melanocyti c lesions is heterogeneous and related to tumor progression, and expre ssion of TGF-beta 2 and of TGF-beta 3 commences at critical junctures during progression of nevi to primary melanomas.