DNA Methylation of HOXD3 as a Marker of Prostate Cancer Progression
TH Van der Kwast, K Kron, V Pethe, L Briollais, B Bapat. University Health Network and University of Toronto, Toronto, Canada; Mount Sinai Hospital, Toronto, Canada
Background: DNA methylation in gene promoters causes gene silencing and is a common event in cancer development and progression. The ability of aberrant methylation events to serve as diagnostic and prognostic markers is being appreciated for many cancers, including prostate cancer. We have previously identified HOXD3 promoter hypermethylation as a potential diagnostic marker for prostate cancer (PCa) through an initial genome-wide CpG island microarray screen of Gleason Score 6 versus 8 cancers in conjunction with validation in a limited independent Pca series.
Design: Using quantitative MethyLight technology, we evaluated the relationship between HOXD3 methylation and clinicopathological paramaters including biochemical recurrence, pathological stage, Gleason score, and Gleason pattern in a series of 232 radical prostatectomies performed between 1998 and 2001 with a follow-up of 10 years. The relationship between average HOXD3 methylation and Gleason score/pattern and stage was analysed. Kaplan Meier analysis were performed to relate conventional parameters and HOXD3 methylation with follow-up.
Results: Biochemical recurrence was associated with HOXD3 methylation in univariate (p-value = 0.043), but not multivariate analysis . HOXD3 methylation was significantly greater in Gleason score 7 cancers versus Gleason score ≤6 cancers (p-value < 0.001) as well pT3a versus pT2 cancers (p-value < 0.001). The proportion of cases with high methylation in Gleason score 7 versus 6 and pT3a versus pT2 were also significantly different (p-values = 0.002 and 0.003, respectively). There were also significant increases in methylation for Gleason pattern 2 versus 3 and for pattern 3 versus 4/5 (paired t-test p-values = 0.01 and < 0.001, respectively).
Conclusions: The results indicate that HOXD3 methylation distinguishes low grade prostate cancers from intermediate and high grade ones and may therefore serve as an important diagnostic biomarker.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 116, Tuesday Afternoon