TELOMERASE ACTIVITY IN HUMAN PROLIFERATIVE BREAST-LESIONS

Telomerase, a cellular reverse transcriptase, has been detected in the majority of human malignant tumors, where it provides an escape mecha nism from proliferative limitations due to progressive telomere erosio n with each cell division. In this study, we used a non-radioactive te lomeric repeat amplification protocol (TRAP) with an internal telomera se assay standard for the detection and semiquantitative analysis of 9 8 single frozen sections of normal breast tissue and benign and malign ant breast lesions on an automated laser-fluorescence sequencer. Telom erase activity was detected in 36 of 40 (90%) infiltrating breast carc inomas, whereas no activity was found in nonmalignant breast tissues i ncluding blunt duct adenosis, papilloma, ductal hyperplasia and atypic al ductal hyperplasia. However, telomerase activity was detected in 59 % of ductal in situ carcinomas, suggesting that telomerase reactivatio n is an early event in breast carcinogenesis. We found a positive corr elation between telomerase activity levels and cell proliferation dete rmined by MIB1 immunostaining. No correlation, however, could be demon strated between telomerase activity and other known breast cancer prog nostic indicators. Telomerase activity was also detected in 60% of fib roadenomas indicating that careful interpretation of analysis of telom erase activity in fine needle aspirates is required, since low telomer ase activity may not necessarily be an indicator of malignancy in brea st tissue.