Molecular and Cellular Biology
Abstract 691: Methylation of APC and GSTP1 in non-neoplastic
tissue adjacent to prostate tumour and mortality from prostate
cancer.
Chiara Celestina Grasso, Lorenzo Richiardi, Valentina Fiano, Daniela Zugna, Anna Gillio Tos, Luisa Delsedime and Franco Merletti
DOI: 10.1158/1538-7445.AM2013-691 Published April 2013
Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC
Abstract
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. The incidence of prostate cancer has increased dramatically since the introduction of prostate-specific antigen (PSA) testing at the end of the 1980s; opportunistic PSA-based screening for prostate cancer is widespread, although its ability to decrease mortality is still being debated.
We studied gene methylation in non-neoplastic tissue adjacent to prostate tumours (NTAT) in association with prostate cancer mortality, as a marker to discriminate between indolent and aggressive prostate tumours.
From 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 prostatic tumour tissues and used probe real-time PCR to analyse methylation of the glutathione S-transferase (GSTP1) and adenomatous polyposis coli (APC) gene promoters. Prevalence of APC and GSTP1 methylation in the NTAT was between 40 and 45%. It was associated with methylation in prostatic tumour tissue for the same two genes as well as with high Gleason. The hazard ratio (HR) of prostate cancer mortality was 2.16 (1.13-4.13) for APC methylation, and 2.83 (1.42-5.65) for GSTP1 methylation in NTAT. It changed to 1.75 (0.95-3.22) and 1.61 (0.80-3.22) after adjusting for Gleason score and methylation in prostatic tumour tissue. Comparison of 2 vs. 0 methylated genes in NTAT revealed a HR of 3.84 (1.83-8.03), which decreased to 2.12 (1.03-4.37) after adjustment. Results were stronger in the first 5 years of follow-up (adjusted HR: 3.03, 95% CI: 1.20-7.67) and in the biopsy sub-cohort (HR: 5.91, 95% CI: 1.00-35.0).
This results show that changes 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.
Citation Format: Chiara Celestina Grasso, Lorenzo Richiardi, Valentina Fiano, Daniela Zugna, Anna Gillio Tos, Luisa Delsedime,
Franco Merletti. Methylation of APC and GSTP1 in non-neoplastic tissue adjacent to prostate tumour and mortality from prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 691. doi:10.1158/1538-7445.AM2013-691
