Telomerase activity in melanocytic lesions - A potential marker of tumor biology

Telomerase activation, being a cardinal requirement for immortalization, is a crucial step in the development of malignancy. With a view toward diagno stic and biological aspects in melanocytic neoplasia, we investigated the r elative levels of telomerase activity in 72 nevi and 16 malignant melanomas by means of a modified telomeric repeat amplification protocol (TRAP) assa y, including an internal amplification standard. We further compared telome rase activity with the expression of two different proliferation-specific p roteins, Ki-67 and repp86, a protein expressed exclusively in the cell cycl e phases S, G2, and M. Telomerase activity was associated with the overall growth fraction (Ki-67) but showed a closer correlation with the expression of repp86. Both telomerase activity and proliferation indices discriminate d deafly between malignant melanomas and nevi, but not between common and d ysplastic nevi. Nonetheless, a portion of nevi exhibited markedly elevated telomerase activity levels without proportionally increased proliferation. This was independent of discernible morphological changes. Clinicopathologi cal correlations showed an association between high telomerase activity and early metastatic spread in melanomas, linking telomerase to tumor biology. Our results provide arguments in favor of an occasional progression from n evi to melanomas and imply that proliferation measurements in combination w ith telomerase assays may help to elicit early malignant transformation tha t is undetectable by conventional morphology.