© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1874-1881, Copyright © 1997 by Oxford University Press
GM Clark, CK Osborne, D Levitt, F Wu and NW Kim
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.
ARTICLES
Telomerase activity and survival of patients with node-positive breast cancer
Department of Medicine, The University of Texas Health Science Center at San Antonio, 78284-7884, USA. gary@oncology.uthscsa.edu
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