Journal
LABORATORY INVESTIGATION
Volume 90, Issue 7, Pages 1060-1067Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2010.57
Keywords
DNA methylation; epigenetics; homeobox; HOXD3; progression; prostate cancer
Categories
Funding
- National Cancer Institute of Canada/Canadian Prostate Cancer Research Initiative [18568]
- Ontario Student Opportunity Trust Fund
Ask authors/readers for more resources
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. Using quantitative MethyLight technology, we evaluated the relationship between HOXD3 methylation and clinicopathological parameters including biochemical recurrence, pathological stage, Gleason score (GS), and Gleason pattern in a series of 232 radical prostatectomies performed between 1998 and 2001. HOXD3 methylation was significantly greater in GS 7 cancers vs GS <= 6 cancers (P-value <0.001) as well as pT3/pT4 vs pT2 cancers (P-value <0.001). The proportion of cases with high methylation in GS 7 vs <= GS 6 and pT3/pT4 vs pT2 were also significantly different (P-values -0.002 and 0.005, respectively). There were also significant increases in methylation from Gleason pattern 2-3 and from pattern 3 to 4/5 (paired t-test P-values = 0.01 and <0.001, respectively), whereas methylation from lymph node metastases was decreased when compared with matched tumor tissue (P-value = 0.029). HOXD3 methylation was associated with biochemical recurrence in univariate analysis (P-value = 0.043) and showed evidence for interaction with pathological stage as a predictor variable in Cox regression analysis (P-value -0.028). The results indicate that HOXD3 methylation distinguishes low-grade prostate cancers from intermediate and high-grade ones and may also have prognostic value when considered together with pathological stage. Laboratory Investigation (2010) 90, 1060-1067; doi: 10.1038/labinvest.2010.57; published online 8 March 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available