Promoter hypermethylation in APC, GSPT1 and RUNX3 and
long-term mortality of prostate cancer patients
Lorenzo Richiardi, Valentina Fiano, Laura De Marco, Loredana Vizzini, Anna Gillio-Tos and Franco Merletti
DOI: Published May 2007
AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA
Abstract
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Recent studies suggested that CpG island hypermethylation at promoter of specific genes may be used to discriminate between malignant and benign prostate disease and correlates with prostate cancer recurrence. We investigated whether detection of CpG island promoter hypermethylation at three genes (APC, GSPT1 and RUNX3) at the time of the cancer diagnosis is associated with
long-term mortality.
We identified 302 consecutive patients diagnosed with prostate cancer at a pathology ward of the main hospital of Turin, Italy, between 1982 and 1988. For each patient, slices of paraffin embedded tumor tissue and information on tumor characteristics reported in the pathology reports were obtained. Adequate genomic DNA was extracted from 232 patients (77%) of the slices. Methylated status was tested using bisulfite modification and methylation specific PCR. Patients with known methylated status were followed-up for mortality until 2006 (12 were lost to follow-up).
Overall, 220 patients were followed up for a median of 3 years (range: 0-22). For each gene, the methylated status was not associated with age at cancer diagnosis or grade of tumor differentiation. Both promoter hypermethylation at APC and the grade of differentiation
were independent predictors of the overall mortality (Table 1). The hazard ratio of overall mortality increased with the number of hypermethylated genes: we found a hazard ratio of 1.62 (95% confidence intervals 1.07-2.45) for three methylated genes compared with one methylated gene (Table 1).
Detection of promoter CpG island hypermethylation at APC and the number of hypermethylated genes at the time of prostate cancer
diagnosis were suggested to be early markers of cancer development independent from the grade of tumor differentiation. Analyses on prostate cancer-specific mortality will be carried out to support these findings. Acknowledgments: this work has been supported by the Italian Association for Cancer Research (AIRC).
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA American Association for Cancer Research
