Quantitative determination of telomerase activity in breast cancer and benign breast diseases

Telomerase plays an important role in maintaining the stability of chromoso mes. This ribonucleoprotein prevents chromosome ends (telomeres) from gradu al loss with each cell division. It enables tumor cells to maintain telomer e length, allowing indefinite replicative capacity. Telomerase activity has been detected in the majority of tumor and germ cells and in immortalized cell lines. Quantitative telomerase PCR-ELISA (TeloTAGGG Telomerase PCR ELISA(PLUS)) wa s evaluated for distinguishing benign and malignant breast tissue. Activity of telomerase was determined in 27 samples of fibrocystic and dysplastic t issues, 28 fibroadenomas and phylloid tumors, and 154 breast cancer tissues ; 59 specimens were analyzed retrospectively. Analytical precision and linearity of the assay was tested using breast car cinoma cell line ZR-75-1 and breast tumor tissue extracts. About 4% of tumo r samples were excluded from analysis due to interferences in the PCR react ion. Relative telomerase activity differed significantly in the groups of d ysplastic tissues, fibroadenomas and carcinomas. The highest activity was f ound in breast cancer tissue. This method can identify breast cancer tissue with 73% clinical sensitivity and 93% specificity as compared to benign br east tumors. We did not find a correlation between telomerase activity and the tissue levels of estrogen and progesterone receptors, HER-2/neu oncopro tein concentration, tumor size, and lymph node positivity. Probability of d isease-free survival was significantly lower for patients with telomerase a ctivity higher than median value. As the assay for telomerase activity has very high analytical sensitivity a nd high specificity for cancer cells, this routinely used method may prove useful for distinguishing malignant phenotype of breast tissues.