EPCA-2 validated as serum prostate cancer marker

October 15, 2008

EPCA-2.19, a second, independent epitope of the EPCA-2 protein, offers extremely high sensitivity and specificity results that are almost identical to those obtained for a first published assay using the EPCA-2.22 epitope.

Orlando, FL-In an ongoing project to develop Early Prostate Cancer Antigen-2 (EPCA-2) as a serum marker for prostate cancer detection, researchers from the Brady Urological Institute, Johns Hopkins Hospital in Baltimore, now report that EPCA-2.19, a second, independent epitope of the EPCA-2 protein, offers extremely high sensitivity and specificity results that are almost identical to those obtained for a first published assay using the EPCA-2.22 epitope.

"Demonstrating that a second test based upon an antibody raised to another distinct region of EPCA-2 has similar characteristics as an initial assay is important for further validating EPCA-2 as a prostate cancer marker and for advancing us toward our long-term goal of using EPCA-2 as a diagnostic serum test for prostate cancer," said first author Eddy S. Leman, PhD, an instructor in urology at Johns Hopkins.

"Now we are in the process of developing a sandwich assay using both epitopes in order to generate a more standardized assay."

The investigation of an ELISA serum assay for EPCA-2.19 was conducted in a study population that included 194 serum samples from 43 healthy men with PSA <2.5 ng/mL, 30 healthy men with PSA ≥2.5 ng/mL and negative prostate biopsy, 33 men with BPH, 43 men with organ-confined prostate cancer, and 45 men with non-organ-confined disease. A control group included 134 samples from healthy females and patients with other benign diseases and cancers other than prostate cancer.

Visual inspection of a scatterplot of the EPCA-2.19 values for the study and control populations showed that an EPCA-2.19 cutoff value of 0.5 ng/mL performed well in separating the prostate cancer patients (with organ-confined and non- organ-confined disease) from the healthy men, men with BPH, and the control population. In a receiver operator curve analysis comparing the normal men and those with BPH to the prostate cancer patients, the ECPA-2.19 assay showed an area under the curve of 0.982.

"EPCA-2.19 at a cutoff of 0.5 ng/mL also had a sensitivity of 91% and a specificity of 94% in separating the normal men and men with BPH from the men with any type of prostate cancer," Dr. Leman reported. "In contrast, PSA using a cutoff of 2.5 ng/mL had a specificity of 67% and sensitivity of 95%."

Additional validation under way

Validation studies are now under way analyzing EPCA-2 (EPCA-2.19 and EPCA-2.22) levels in serum samples from several sources, including the multi-center samples from the National Cancer Institute's Early Detection Research Network. In addition, researchers are investigating levels of EPCA-2 in serum of men with prostate cancer prior to and while undergoing therapeutic interventions, including hormonal therapy, radiation, and chemotherapy, and they are using the enrolled cohort of the Baltimore Longitudinal Study of Aging to investigate EPCA-2 levels in a population of aging men.

Studies also are planned to characterize the kinetics of the protein, including velocity and doubling time.

"Although there is still work to be done, these recent studies provide us with additional evidence regarding the potential utility of a blood test for EPCA-2," Dr. Getzenberg, the Donald S. Coffey Professor and director of urology research at Johns Hopkins, told Urology Times. "We have now analyzed samples from over 1,200 men, and the data continue to be encouraging."

Dr. Getzenberg is a former consultant/adviser to Onconome, Inc.