Telomerase activity and expression of apoptosis and anti-apoptosis regulators in the progression pathway of human melanoma.

The stages defining the progression pathway of human melanoma are atypical nevi, the precursor lesions and risk markers of melanoma, melanoma in situ and melanoma in the radical growth phase (RGP), which represent the early stages of melanoma development, and primary melanoma in the vertical growth phase (VGP) and melanoma in the metastatic growth phase (MGP), which are the advanced stages of the disease. Unlike cells obtained from VGP and MGP melanomas, which can be established as cell lines, cells derived from atypical nevi, melanoma in situ, and RGP melanoma cannot be propagated in vitro. Thus, information regarding molecular markers that may be differentially expressed in the early versus the advanced stages of this disease can only be obtained from the analysis of specimens. Since activation of telomerase and deregulation of apoptosis contribute to the pathogenesis of a significant number of human malignancies, we conducted a study, using nevus and melanoma specimens, to determine at what stage in the progression pathway of melanoma, telomerase activity can first be detected, and whether concordant with telomerase activation, one might observe a stage-specific switch from expression of promoters to inhibitors of apoptosis. The findings described here, demonstrate telomerase activity in some but not all MGP melanomas and not in any of the preceding pathological stages, and no apparent imbalance between pro- and anti-apoptotic markers in telomerase-positive MGP melanomas compared to telomerase-negative nevi and telomerase-negative VGP and MGP melanomas.