T e l o m e r a s e E x p r e s s i o n i n H u m a n B r e a s t C a n c e r W i t h a n d Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto the ends of chromosomes, thereby preventing the replication-dependent shortening of these ends. Telomerase activity is detected in a wide range of cancers of various tissues, and its expression may be a critical step in tumor progression. The telomeric repeat amplification protocol was used to compare telomerase activity in breast cancers with and without lymph node metastases, as well as in fibroadenomas and normal breast tissue. Expression of telomerase was detected in 22 (79%) of 28 primary breast cancers, which included 16 (73%) of 22 cancers positive and 6 (100%) of 6 cancers negative for axillary lymph node metastases. It was detected in 1 (11%) of 9 fibroadenomas but was negative in 13 normal breast tissues. There was no statistical difference in expression of telomerase between axillary node-negative primary breast cancers and similar tumors with nodal metastasis (P = .289). Further, no statistical association was found between telomerase activity and tumor size (P = .679) or hormonal status (P =.178). The difference in telomerase activity among breast cancers vs fibroadenomas and normal breast tissues, however, was statistically significant (P < .001). Although normal breast tissue does not express telomerase, both node-positive and node-negative breast cancers express telomerase. Telomerase is an essential ribonucleoprotein polymerase that a d d s telomeric DNA to the ends of eukaryotic chromosomes. 1-3 The RNA component of h u m a n telomerase, designated hTR, was recently cloned and sequenced. 4 Telomeres are specialized structures at the ends of eukaryotic chromosomes that appear to function in the protection, positioning, and replication of chromosomes. In human beings, the DNA sequence of telomeres consists of a guaninerich tandem repeat, ie, (TTAGGG) n . As normal cells divide, the replicating DNA loses a number of these repeats. Shortening of the telomere length to less than Manuscript received luly 30, 1996; revision accepted October 10,1996. W i t h o u t L y m p h N o d e M e t a s t a s e sAddress reprint requests to Dr Nawaz: Department of Pathology, B-216, University of Colorado Health Sciences Center, 4200 East Ninth Ave, Denver, CO 80262. a critical level creates a signal that stops the cell from dividing; this event is followed by cell senescence and death. Several investigators recently have shown telomerase activity in malignant tissues of various anatomic sites but not in the corresponding normal tissue; these findings suggest that this activity may be a marker for malignancy. 5Breast cancer remains the second most common cause of death in women. The most important prognostic indicator in invasive breast cancer is the presence of axillary lymph node metastases 6 ; however, molecular markers of tumor progression have failed to identify which cases of invasive breast cancer are at greatest risk for nodal metastases at t...