Global hypomethylation is common in prostate cancer cells: A quantitative predictor for clinical outcome?

Arthur R. Brothman, Gregory Swanson, Teresa M. Maxwell, Jiang Cui, Kelley J. Murphy, Jennifer Herrick, V. O. Speights, Jorge Isaac, L. Ralph Rohr

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-36
Number of pages6
JournalCancer Genetics and Cytogenetics
Volume156
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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