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Telomere DNA Content in Prostate Biopsies Predicts Early Rise in Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer - 20/08/11

Doi : 10.1016/j.urology.2009.04.032 
Eric G. Treat a, b, Christopher M. Heaphy c, Larry W. Massie d, Marco Bisoffi c, e, Anthony Y. Smith a, e, Michael S. Davis a, f, Jeffrey K. Griffith a, c, e, ⁎
a Department of Surgery, Division of Urology, University of New Mexico School of Medicine, Albuquerque, New Mexico 
b General Clinical Research Center, University of New Mexico Hospital, Albuquerque, New Mexico 
c Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico 
d Department of Pathology, Raymond G. Murphy Department of Veterans Affairs Medical Center in Albuquerque, New Mexico 
e Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 
f Department of Surgery, Division of Urology, Veterans Affairs Medical Center in Albuquerque, New Mexico 

Reprint requests: Jeffrey K. Griffith, PhD, Department of Biochemistry and Molecular Biology, MSC 08 4670, 1 University of New Mexico, Albuquerque, NM 87131-0001

Resumen

Objective

To determine whether measurement of telomere DNA content (TC) in prostate biopsy tissue predicts prostrate-specific antigen (PSA) recurrence in men after undergoing radical prostatectomy for prostate cancer.

Methods

Slot blot titration assay was used to quantitate TC in archived diagnostic prostate needle biopsy specimens for subjects (n = 103) diagnosed with prostate cancer and who subsequently underwent radical prostatectomy between 1993 and 1997. TC was compared to the clinical outcome measure; PSA recurrence, defined as an increase in PSA ≥ 0.2 ng/mL on 2 or more consecutive measurements post-prostatectomy, was observed retrospectively, for a mean follow-up period of 114 months (range, 1-165).

Results

In the cohort, 46 subjects had a PSA recurrence. In a univariate Cox proportional hazards model, low TC (<0.3 of standard) demonstrated a significant risk for PSA recurrence (HR = 1.94; 95% CI: 1.02-3.69, P = .04). In a subset analysis of men with biopsy Gleason sum ≤ 6 (n = 63; 25 recurrences), a univariate Cox proportional hazards model demonstrated that low TC had a greater risk of PSA recurrence (HR = 4.53; 95% CI: 2.00-10.2, P < .01). In a multivariate Cox proportional hazards model, low TC was also significantly associated with PSA recurrence in this subset after controlling for preoperative PSA levels (HR = 6.62; 95% CI: 2.69-16.3, P < .01).

Conclusions

Low TC measured in prostate biopsy tissue predicts early likelihood of post-prostatectomy PSA recurrence in a retrospective analysis, and in men with biopsy Gleason sum ≤ 6 disease it is also independent of preoperative PSA level.

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Esquema


 Eric G. Treat and Christopher M. Heaphy contributed equally to this study.
 Supported by National Institutes of Health Grant RR0164880 (to M. B. and J. K. G.), Department of Defense pre-doctoral training awardW81XWH-05-0273 (to C. M. H.), University of New Mexico Cancer Center Support Grant NIH/NCI P30CA118110, and the University of New Mexico General Clinical Research Center (NIH NCRR GCRC Grant M01-RR00997) (to E. G. T.).


© 2010  Elsevier Inc. Reservados todos los derechos.
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Vol 75 - N° 3

P. 724-729 - mars 2010 Regresar al número
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