Analysis of telomerase activity levels in breast cancer: positive detection at the in situ breast carcinoma stage.
Telomerase activity has been implicated to be associated with most human malignant tumors, including breast cancer. To evaluate possible associations with well-known prognostic factors in breast cancer, we performed a semi-quantitative analysis of telomerase activity levels using the very sensitive PCR-mediated telomeric repeat amplification protocol. Telomerase activity was detected in 99 of 104 breast cancer samples analyzed (95.2%), whereas no activity was detected in 10 of 10 adjacent nonmalignant breast tissues. Analysis of five breast fibroadenoma samples revealed telomerase activity in one (20%). In contrast to previous observations, we observed that 100% of stage I breast tumors were positive for telomerase activity. More interestingly, we detected telomerase activity in six of six ductal carcinoma in situ samples (i.e., stage 0). In our semiquantitative analysis of levels of enzymatic activity, we found no statistically significant correlation at the P < h 0.05 level between telomerase levels and lymph node metastasis status, estrogen and progesterone receptor status, tumor size, S-phase fraction, and ploidy. The only statistically significant correlation was found with patient age (rho = -0.3; P = 0.03). We observed no statistically significant difference in the telomerase activity levels of early tumors (stages 0 and 1) versus more advanced lesions (stages II to IV). Nevertheless, stage IV tumors displayed a tendency for higher telomerase activity levels. In summary, no clear association was observed between telomerase levels and known breast cancer prognostic indicators. However, telomerase detection by the telomeric repeat amplification protocol method, due to its high sensitivity, may be of value in early breast cancer diagnosis and detection, because our data indicate that telomerase reactivation appears to constitute a relatively early event in breast carcinogenesis.
Bednarek
A K
AK
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA.
Sahin
A
A
Brenner
A J
AJ
Johnston
D A
DA
Aldaz
C M
CM
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000201:enzymology*; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000201:enzymology*; D006801:Humans; D009367:Neoplasm Staging; D011379:Prognosis; D019098:Telomerase / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D019098:Telomerase