Abstract
BackgroundMarkers that can discriminate between indolent and aggressive prostate tumours are needed. We studied gene methylation in non-neoplastic tissue adjacent to prostate tumour (NTAT) in association with prostate cancer mortality.MethodsFrom two cohorts of consecutive prostate cancer patients diagnosed at one pathology ward in Turin, Italy, we selected 157 patients with available NTAT and followed them up for more than 14 years. We obtained DNA from NTAT in paraffin-embedded prostate tumour tissues and used probe real-time PCR to analyse methylation of the glutathione S-transferase (GSTP1) and adenomatous polyposis coli (APC) gene promoters.ResultsPrevalence of APC and GSTP1 methylation in the NTAT was between 40 and 45%. It was associated with methylation in prostate tumour tissue for the same two genes as well as with a high Gleason score. The hazard ratio (HR) of prostate cancer mortality was 2.38 (95% confidence interval: 1.23–4.61) for APC methylation, and 2.92 (1.49–5.74) for GSTP1 methylation in NTAT. It changed to 1.91 (1.03–3.56) and 1.60 (0.80–3.19) after adjusting for Gleason score and methylation in prostate tumour tissue. Comparison of 2 vs. 0 methylated genes in NTAT revealed a HR of 4.30 (2.00–9.22), which decreased to 2.40 (1.15–5.01) after adjustment. Results were stronger in the first 5 years of follow-up (adjusted HR: 3.29, 95% CI: 1.27–8.52).ConclusionsChanges in gene methylation are an early event in prostate carcinogenesis and may play a role in cancer progression. Gene methylation in NTAT is a possible prognostic marker to be evaluated in clinical studies.
Highlights
Prostate cancer is the most common tumour in men in many populations, with a crude incidence of 120–130 per 105 in Europe and the United States [1]
We found that adenomatous polyposis coli (APC) methylation in prostate tumour tissue was associated with a 50% increased risk of mortality from prostate cancer
In this paper we investigated if methylation changes in the nonneoplastic tissue adjacent to prostate tumour (NTAT) are associated with prostate cancer prognosis
Summary
Prostate cancer is the most common tumour in men in many populations, with a crude incidence of 120–130 per 105 in Europe and the United States [1]. The high prevalence of indolent prostate cancer and the use of opportunistic PSA-based screening for prostate cancer may lead to over-treatment. We found that APC (adenomatous polyposis coli) methylation in prostate tumour tissue was associated with a 50% increased risk of mortality from prostate cancer. Methylation of GSTP1 (glutathione S-transferase) promoter is the most extensively investigated epigenetic change in prostate cancer. It can be found in more than 80% of prostate cancers, with a lower prevalence in benign tissue [15]; it is strongly associated with Gleason score but its prognostic role independent of Gleason score is unclear [5]. We studied gene methylation in non-neoplastic tissue adjacent to prostate tumour (NTAT) in association with prostate cancer mortality
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