Sensitive Detection Of Abnormally Methylated Cpg Islands As A Prostate Cancer Biomarker

The use of serum assays for prostate-specific antigen (PSA) for prostate cancer screening has drastically changed the natural history of prostate cancer. Most men now typically diagnosed with nonpalpable, localized, prostate cancer are amenable to treatment with surgery or radiation therapy (46). However, PSA screening is far from perfect. Findings of the Prostate Cancer Prevention Trial, in which men who entered the study with a "normal" serum PSA level were subjected to prostate biopsy at the end of the trial, revealed prostate cancer in 24.4% of the men treated with a placebo, with cancer in 6.6% of men who had a serum PSA of less than 0.5 ng/mL (47,48). Prostate biopsies are also less than perfect. The current ultrasound-guided biopsy strategy features random sampling of prostate tissue, rather than some sort of image-directed approach to detect prostate cancer. The optimal number of random tissue samples needed for accurate detection of clinically significant prostate cancer remains controversial (49,50). This tendency toward under-diagnosis, that is, missing prostate cancer when present, also seems to be accompanied by a general fear of over-diagnosis, that is, discovering and treating non-life-threatening prostate cancer and causing detrimental effects on quality of life (Fig. 4). Finally, although histological examination of prostate tissues enables accurate diagnosis of prostate cancer, distinct from other microscopic prostate abnormalities, and

Table 1

Genes Assessed for CpG Island Hypermethylation Changes in Prostate Cancer Tissues a

Table 1

Genes Assessed for CpG Island Hypermethylation Changes in Prostate Cancer Tissues a

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