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Telomerase Activity and Survival of Patients With Node-Positive Breast Cancer
- Source :
- JNCI Journal of the National Cancer Institute. 89:1874-1881
- Publication Year :
- 1997
- Publisher :
- Oxford University Press (OUP), 1997.
-
Abstract
- Background Shortening of telomeres (specialized structures at the ends of chromosomes) beyond a certain length may signal a cell to stop dividing and to enter senescence. A ribonucleoprotein enzyme, telomerase, is a key component in maintaining telomere length. Because the majority of cancers express telomerase but most normal somatic tissues do not, we measured the level of telomerase expression in primary breast cancer specimens for correlation with traditional prognostic indicators and disease outcome. Methods Telomerase activity was measured in frozen human breast cancer specimens by use of the Telomeric Repeat Amplification Protocol (TRAP) assay. The level of telomerase activity was expressed as total product generated (TPG) and was corrected for specimen cellularity by expressing it as a ratio of TPG to the sample's 28S ribosomal RNA content. Results A preliminary study of 150 breast cancer specimens demonstrated that telomerase activity correlated with the fraction of cells in S phase of the cell cycle (r(sp) = .23). In a larger prognostic study of 398 tumors from patients with lymph node-positive breast cancer, telomerase expression correlated with S-phase fraction, progesterone receptor level, DNA ploidy, and lymph node status. After correcting for sample cellularity, increasing TPG levels were associated with decreased disease-free survival (P = .041) and overall survival (P = .009) of the patients. The telomerase activity level remained strongly predictive of death (P = .027) and marginally predictive of disease recurrence (P = .08) after adjustment for other prognostic factors. All P values are two-sided. Conclusions Telomerase activity in human breast cancers is associated with a more aggressive tumor phenotype in patients.
- Subjects :
- Adult
Cancer Research
Pathology
medicine.medical_specialty
Telomerase
Mitotic index
Breast Neoplasms
Biology
Disease-Free Survival
Breast cancer
Predictive Value of Tests
Risk Factors
Progesterone receptor
medicine
Humans
Lymph node
Repetitive Sequences, Nucleic Acid
Ribonucleoprotein
Analysis of Variance
Cancer
Middle Aged
Prognosis
medicine.disease
Survival Analysis
Telomere
medicine.anatomical_structure
Oncology
Lymphatic Metastasis
Cancer research
Female
Subjects
Details
- ISSN :
- 14602105 and 00278874
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- JNCI Journal of the National Cancer Institute
- Accession number :
- edsair.doi.dedup.....f67a1e9a9df7edc9a9197fbcc83471a4