TELOMERASE ENZYME-ACTIVITY AND RNA EXPRESSION DURING THE MULTISTAGE PATHOGENESIS OF BREAST-CARCINOMA

Telomerase, an RNA-containing enzyme, is associated with cellular immo rtality and malignancy. We investigated the role of telomerase during the multistage pathogenesis of breast cancer, We used the semiquantita tive, PCR-based telomeric repeat amplification protocol assay for enzy me activity (42 specimens from 42 patients) and a radioactive in situ assay for expression of its RNA component (human telomerase RNA; hTR) for the identification of telomerase-positive cells in archival resect ion samples (n = 67 from 39 patients). Low telomerase activity was det ected in 1 (14%) of 7 samples of benign breast disease, in 4 (67%) of 6 fibroadenomas, in 11 (92%) of 12 carcinoma in situ (CIS) lesions, an d in 16 (94%) of 17 invasive breast cancers. There was a progressive i ncrease in the mean telomerase levels with progressive increase in sev erity of histopathological change (P < 0.05). Almost all of 67 resecti on samples expressed hTR, irrespective of histology. Expression was lo w to moderate in some samples of normal epithelium and nonproliferativ e fibrocystic changes, hTR expression was limited to epithelial cells; expression in stromal cells, including those in fibroadenomas, was ne gative. Increased hTR expression was observed in some foci of apocrine metaplasia and atypical hyperplasia. Increased hTR expression was als o observed in all CIS and invasive lesions, although considerable hete rogeneity was noted. Focal up-regulation was frequently noted in CIS l esions in the vicinity of invasive tumors. Thus, up-regulation of hTR may be a predictive marker for invasive tumor development.