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.
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: Bruce J Trock; Michelle J Brotzman; Leslie A Mangold; Joseph W Bigley; Jonathan I Epstein; David McLeod; Eric A Klein; J Stephen Jones; Songbai Wang; Theresa McAskill; Jyoti Mehrotra; Bhargavi Raghavan; Alan W Partin Journal: BJU Int Date: 2011-11-11 Impact factor: 5.588
Authors: Benjamin A Rybicki; Andrew Rundle; Oleksandr N Kryvenko; Nicoleta Mitrache; Kieu C Do; Michelle Jankowski; Dhananjay A Chitale; Sheri Trudeau; Steven A Belinsky; Deliang Tang Journal: Int J Cancer Date: 2016-03-02 Impact factor: 7.396
Authors: Matthew Truong; Bing Yang; Andrew Livermore; Jennifer Wagner; Puspha Weeratunga; Wei Huang; Rajiv Dhir; Joel Nelson; Daniel W Lin; David F Jarrard Journal: J Urol Date: 2012-11-15 Impact factor: 7.450
Authors: Deliang Tang; Oleksandr N Kryvenko; Nicoleta Mitrache; Kieu C Do; Michelle Jankowski; Dhananjay A Chitale; Sheri Trudeau; Andrew Rundle; Steven A Belinsky; Benjamin A Rybicki Journal: J Urol Date: 2013-01-30 Impact factor: 7.450
Authors: Lissette Delgado-Cruzata; Gregory W Hruby; Karina Gonzalez; James McKiernan; Mitchel C Benson; Regina M Santella; Jing Shen Journal: DNA Cell Biol Date: 2011-08-10 Impact factor: 3.550