Association between Telomerase Activity, Cell Cycle Regulators, and Histopathological Prognostic Parameters in Breast Cancer

Kim, In Hu; Lee, Soo Jung; Lee, Joo Hyung; Jeong, Ki Ho; Kwun, Koing Bo; Kim, Dong Seok; Baek, Seok Hwan

Abstract

PURPOSE: Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto the ends of chromosomes, thereby preventing the replication-dependent shortening of those ends. This enzyme is essential for stability of eukaryotic chromosomes and may be necessary for cell immortalization. Telomerase activity is detected in a wide range of cancers of various tissues, and its expression may be a critical step in tumor progression. METHODS: The telomerase activity was measured using a telomeric repeat amplification protocol (TRAP) assay in 65 cases of breast cancers, 9 cases of fibroadenomas, and 7 cases of normal breast tissues. To compare the telomerase activity with cell cycle regulators, we measured the expression of the cyclin D1 and the p53 proteins by using immunohistochemical analysis. To compare the telomerase activity with traditional prognostic indicators, we measured the ER, PR, c-erbB-2 and ki-67 expression by using immunohistochemical analysis. Disease-free survival and overall survival in relation to telomerase activity were studied by using the Kaplan-Meier method. RESULTS: Telomerase activity was detected in 42 (64.6%) of the 65 breast cancers, 4 (44.4%) of the 9 fibroadenomas, and in none of the 7 normal breast tissues. There was no significant relationship between telomerase activity and cell cycle regulators such as cyclin D1 or p53. There was no statistical correlation between telomerase activity and tumor size, lymph nodal status, or histopathological prognostic parameters, such as ER, PR, p53, c-erbB-2 and ki-67, but a significant correlation was found (p=0.006) between telomerase activity and histologic grade. The telomerase activity was not significantly correlated with either the overall survival or the disease-free survival. CONCLUSION: These results suggest that telomerasemay play a role in the malignant transformation of breast tissue and that this enzyme was more activated in cancers of a poor histologic grade. However, the telomerase activity was not related to cell cycle regulators and traditional prognostic parameters. The possible significance of telomerase activity in breast cancer remains open to further investigation.