Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome?
This study was designed to determine if cytological detection of 5-methylcytosine (5MC) was feasible on prostate tumor sections and to determine if levels of 5MC differed in malignant compared to normal prostate tissue. We further sought to see if 5MC levels correlated with any clinical outcome data. Thirty prostate tumor sections were obtained from patients who underwent radical prostatectomies from 1988 to 1995; these represented a mix of low to high grade tumors. Clinical data were maintained for each of these patients with a minimum of 7 years of follow up. Sections were stained with a commercially available antibody to 5MC and immunocytochemistry levels were subsequently quantified using a computer-assisted true-color imaging system. Tumor and benign regions of the same archived sections were compared, in addition to a series of 12 normal prostate samples. Prostate cancer cells exhibited a pronounced global decrease in methylation compared with benign and normal tissue. This was observed in 29 of 30 patients (96.7%) studied and densitometric scanning of methylation staining indicated that this value was quantifiable. Overall, higher methylation values were detected in men who had positive surgical margins and recurrent disease. These data suggest that loss of methylation is a feature of prostate cancer, and partial gain of methylation (presumably at promoters of specific genes) is associated with clinical outcome and is measurable using whole-cell assays.
Brothman
Arthur R
AR
Department of Pediatrics, University of Utah School of Medicine, 1C210 SOM, 30 North 1900 East, Salt Lake City, UT 84132-2117, USA. art.brothman@genetics.utah.edu
Swanson
Gregory
G
Maxwell
Teresa M
TM
Cui
Jiang
J
Murphy
Kelley J
KJ
Herrick
Jennifer
J
Speights
V O
VO
Isaac
Jorge
J
Rohr
L Ralph
LR
D044503:5-Methylcytosine / Q000276:immunology / Q000378:metabolism*; D000368:Aged; D019175:DNA Methylation; D003720:Densitometry / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
D044503:5-Methylcytosine