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


CONCLUSIONS
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.
Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany. isabel.steiner@charite.de
Isabel
I
Steiner
Klaus
K
Jung
Philipp
P
Schatz
Torsten
T
Horns
Daniel
D
Wittschieber
Michael
M
Lein
Manfred
M
Dietel
Andreas
A
Erbersdobler
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D055088:Early Detection of Cancer; D051549:Glutathione S-Transferase pi / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D019048:Prostatic Intraepithelial Neoplasia / Q000175:diagnosis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000097577:Homeobox Protein PITX2
D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; D051549:Glutathione S-Transferase pi; D018398:Homeodomain Proteins; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C555337:APC protein, human; C540966:retinoic acid receptor, beta2, human; C496556:GSTP1 protein, human