Gene promoter methylation and its potential relevance in early prostate cancer diagnosis.

Abstract

AIMS:

We investigated hypermethylation of the glutathione S-transferase pi (GSTP1), retinoic acid receptor β2 (RARβ2), adenomatous polyposis coli (APC) and paired-like homeodomain transcription factor 2 (PITX2) gene promoters which could serve as a sensitive tool to indicate a risk of prostate cancer even in histologically tumor-free tissues.

METHODS:

Tumor tissues and non-neoplastic tissues at variable distances from the tumor foci were retrieved from 25 formalin-fixed and paraffin-embedded prostatectomy specimens and subjected to DNA extraction. The methylation levels were assessed by means of different assay technologies.

RESULTS:

Significantly increased methylation levels in cancer specimens were found for all promoter regions (GSTP1: 21/25, 84%; RARβ2: 24/25, 96%; APC: 21/25, 84%; PITX2: 20/25, 80%) and in most samples containing prostatic intraepithelial neoplasia. Several samples showed increased RARβ2 and APC methylation in adjacent non-neoplastic tissue. An association between the methylation extent of GSTP1, APC and RARβ2, respectively, and primary Gleason grade was detectable. GSTP1 methylation was also associated with extraprostatic tumor extension.

CONCLUSION:

GSTP1, APC, RARβ2 and PITX2 methylation occur frequently in prostate cancer, making these markers sensitive tools for the detection of neoplastic lesions in the prostate. For RARβ2, the results suggest a kind of methylation field effect which could be helpful for the detection of prostate cancer. Larger studies are necessary to investigate a potential correlation of GSTP1, RARβ2 and APC hypermethylation with tumor aggressiveness.

• Authors: Isabel Steiner, Klaus Jung, Philipp Schatz, Torsten Horns, Daniel Wittschieber, Michael Lein, Manfred Dietel, Andreas Erbersdobler
• Journal: Pathobiology : journal of immunopathology, molecular and cellular biology (Pathobiology) Vol. 77 Issue 5 Pg. 260-6 ( 2010) ISSN: 1423-0291 [Electronic] Switzerland
• PMID: 21116117 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 S. Karger AG, Basel.

Chemical References

• APC protein, human
• Adenomatous Polyposis Coli Protein
• Biomarkers, Tumor
• Homeodomain Proteins
• Receptors, Retinoic Acid
• Transcription Factors
• retinoic acid receptor, beta2, human
• GSTP1 protein, human
• Glutathione S-Transferase pi

Topics

• Adenomatous Polyposis Coli Protein (genetics)
• Aged
• Biomarkers, Tumor (genetics)
• DNA Methylation
• Early Detection of Cancer
• Glutathione S-Transferase pi (genetics)
• Homeodomain Proteins (genetics)
• Humans
• Male
• Middle Aged
• Promoter Regions, Genetic
• Prostatic Intraepithelial Neoplasia (diagnosis, genetics)
• Prostatic Neoplasms (diagnosis, genetics)
• Receptors, Retinoic Acid (genetics)
• Transcription Factors (genetics)
• Homeobox Protein PITX2