Discerning Prostate Cancer Bio Markers

Urologists rely upon prostate-specific antigen (PSA) and other biomarkers for diagnosing and monitoring prostate cancer. But – call us greedy – we have always wished they were a little more discerning. Ideally, biomarkers would allow us to selectively identify patients with high risk of recurrence, those who could benefit from intervention, and those who can reasonably choose active surveillance.

Finally, however, we may get our wishes granted. Scientists from the the Institute of Pathology at University Hospital Bonn in Germany have discovered a biomarker, PITX2 DNA methylation, which is capable of distinguishing cancerous tissue from non-cancerous tissue and predicting the risk of cancer recurrence using only small amounts of tissue obtained from core needle biopsies.

"Previous studies have shown that aberrant PITX2 methylation is a strong prognostic marker for disease progression in breast and lung cancer. In prostate cancer, several studies have demonstrated that PITX2 hypermethylation is an independent prognosticator of biochemical recurrence following radical prostatectomy. However, none of these studies were conducted on presurgical biopsies," explained Glen Kristiansen, MD, one of the authors.

The scientists measured PITX2 methylation biomarker levels in 24 tumor samples, 24 normal adjacent prostate tissue, and 22 samples with benign prostatic hyperplasia. PITX2 promoter methylation was found to be much, much higher in the actual cancer samples compared to matched normal and benign prostatic hypertrophy tissues.

"These findings demonstrate that the PITX2 biomarker discriminates between prostate cancer and non-cancerous tissue," wrote Dr. Kristiansen.

Researchers then examined whether PITX2 methylation could predict biochemical recurrence within a group of 300 prostate cancer patients who had undergone radical prostatectomy. Again, they discovered that patients with high PITX2 methylation were at significantly increased risk for recurrence.

Later, the biomarker was applied to the core biopsies of 32 patients with prostate cancer and 31 patients with benign prostatic disease. Investigators found that 95 percent of 753 biopsy cores from 63 patients could be analyzed. PITX2 methylation was significantly higher in tumor-positive biopsies and strongly correlated with prostate cancer severity.

"This study not only confirms the prognostic value of PITX2 methylation in prostate cancer, but it also demonstrates its applicability to prostate biopsies. This enables us to plan further studies that may finally translate this biomarker into clinical practice with the aim of further individualizing treatment strategies," noted Dr. Kristiansen.

The research was published in The Journal of Molecular Diagnostics.