Anthony Y Smith | PubMed Health

PubMed2005

Association between cancer-free survival and telomere DNA content in prostate tumors.

PURPOSE: We evaluated the hypothesis that telomere DNA content (TC) in prostate tumor tissue is associated with time to prostate cancer recurrence. MATERIALS AND METHODS: The cohort was comprised of 77 men who underwent prostatectomy between 1982 and 1995. Slot blot assay was used to measure TC in DNA extracted from paraffin embedded tumor and nearby, histologically normal prostate (NHN) tissues. Multivariate Cox proportional hazards analysis was done to relate TC, patient age at diagnosis, Gleason sum and pelvic node involvement to time of prostate cancer recurrence. Regression analysis was done to relate TC in paired tumor and NHN tissues. Nonparametric Kruskal-Wallis analysis was done to relate TC in tumor and NHN tissues with 72-month disease-free survival. RESULTS: TC was a predictor of time to prostate cancer recurrence when controlling for age at diagnosis, Gleason sum and pelvic node involvement (RH = 5.02, 95% CI 1.40 to 17.96, p = 0.0132). TC in tumor tissue was associated with TC in NHN tissue (R = 0.601, p <0.0001). Median TC in tumor and NHN tissues from men in whom cancer recurred within 6 years was approximately half that in men who remained disease-free (p = 0.012 and 0.024, respectively). CONCLUSIONS: Decreased TC in prostate tissues obtained by radical prostatectomy predicts prostate cancer recurrence independent of age at diagnosis, Gleason sum and pelvic node involvement. TC in tumor tissue is also associated with TC in NHN prostate tissue. Thus, mechanisms known to generate genomic instability are operative in fields of cells beyond the tumor margins prior to histological changes.

Aged↗

PubMed2005

A decrease in 1H nuclear magnetic resonance spectroscopically determined citrate in human seminal fluid accompanies the development of prostate adenocarcinoma.

PURPOSE: Because human prostatic fluid contributes almost 50% of the volume of seminal plasma and this fluid contains unique prostatic metabolites such as citrate, which are markedly altered during tumorigenesis, we investigated high resolution H nuclear magnetic resonance (NMR) spectroscopy of unprocessed human seminal plasma as a rapid, noninvasive diagnostic tool for prostate adenocarcinoma. MATERIALS AND METHODS: Semen and prostatic massage samples from control and tumor bearing subjects were stored frozen at -20C and thawed prior to water suppressed NMR analysis. We found that freezing produced no significant alterations in the semen NMR spectra. Quantitative NMR spectroscopy was performed by first calibrating the water suppression data acquisition sequence with a series of standard samples containing known amounts of citrate within the physiological range. RESULTS: Well resolved citrate resonances from the seminal plasma of 3 control subjects with prostate specific antigen (PSA) less than 1 ng/ml were integrated to give concentrations of 97 to 178 mM. Semen from a 47-year-old man with benign prostatic hyperplasia and a PSA of 5.5 ng/ml contained 156 mM citrate. In contrast, seminal plasma from 2 patients with prostate cancer, including a 46-year-old man with Gleason grade 8 and PSA 45.2 ng/ml, and a 64-year-old man with grade 6 and PSA 13.0 ng/ml, revealed citrate NMR signals corresponding to a concentration of only 28 and 24 mM, respectively. Spectra from prostatic massage fluid from a normal 23-year-old volunteer showed a citrate of 483 mM, while massage fluid from a 56-year-old patient with Gleason grade 4 cancer showed a citrate of only 1.35 mM. CONCLUSIONS: To our knowledge this study is the first to use high resolution NMR of semen to diagnose prostate cancer. Given the known effects of adenocarcinoma on prostate metabolism, the study indicates that high resolution H NMR can be used to measure citrate in seminal fluid, potentially providing a new, rapid, noninvasive screening method.

Adenocarcinoma↗