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 has been described in a report in The Journal of Molecular Diagnostics.
Prostate-specific antigen (PSA) and other biomarkers are essential
tools for diagnosing and monitoring prostate cancer. However, biomarkers
to selectively identify patients with high risk of recurrence, those
who might benefit from intervention, and those who can safely choose
active surveillance, are lacking.
‘The prognostic value of PITX2 methylation in prostate cancer and its applicability to prostate biopsies has been demonstrated in this study.’
"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, of the Institute of Pathology at the University
Hospital Bonn (Germany).
This is the first study to determine whether
PITX2 methylation can be used for individualized risk assessment of
prostate cancer using core biopsy tissue.
Investigators measured PITX2 methylation biomarker levels using a
quantitative real-time PCR assay in 24 tumor samples, 24 normal adjacent
prostate tissue, and 22 samples with benign prostatic hyperplasia.
PITX2 promoter methylation was found to be significantly higher in
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," noted Dr. Kristiansen.
Researchers then examined whether PITX2 methylation could predict
biochemical recurrence (two consecutive rises of serum PSA > 0.2
ng/mL) within a group of 300 prostate cancer patients who had undergone
radical prostatectomy. They found that patients with high PITX2
methylation were at significantly increased risk for recurrence.
Subsequently, the biomarker was applied to the core biopsies of 32
patients with prostate cancer and 31 patients with benign prostatic
disease. The core needle biopsy, the most common type of prostate
biopsy, is performed by inserting a needle into the prostate to remove a
small cylinder of tissue. Investigators found that 95% 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 as indicated by the International Society
of Urological Pathology grading system.
Whether a patient with prostate cancer detected by elevated PSA
should be treated pharmacologically, radiotherapeutically, or surgically
is controversial, especially because of concerns about side effects and
in light of recent data that intervention may not affect mortality
within the first ten years.
"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,"
commented Dr. Kristiansen.