New Forms of PSA Under Study at USRF

We know that the PSA test is not specific for prostate cancer, but two isoforms of PSA---proPSA and BPSA, currently under development in a collaboration between USRF and the Hybritech Division of Beckman Coulter---may help improve specificity of the test.

BPSA LOCALIZATION WITHIN THE PROSTATE

Leonard S Marks, Arlyn S Llanes, John W Fan, Stephen D Mikolajczyk, Lisa S Millar, Harry J Linton, William A Munroe, Harry G Rittenhouse, Lori J Sokoll, Daniel W Chan and Alan W Partin.

Abstract to be presented at the Annual AUA Meeting in Orlando, FL in May, 2002.

Introduction and Objectives:
BPSA has been associated with transition zone (TZ) nodularity of BPH, but no direct measurement of BPSA levels in nodule tissue has yet been reported. Thus, concentration of PSA and BPSA were measured in samples of pure BPH nodular and non-nodular tissue.

Methods:
10 men (mean age = 68 ± 6 y.o.) underwent enucleation (N=2) or radical prostatectomy (N=8), and the fresh prostate specimens (mean weight = 84 ± 44 gm) were selectively sampled of tissue (~100 mg) from peripheral (PZ) and transition zone (TZ), taking tissue from 2 nodules (A, B) and non-nodular tissue separately. All samples were histologically benign. Samples were frozen (-70°C), then batch-analyzed, after homogenization and HPLC separation, via dual monoclonal immunoassays with high specificity for PSA and BPSA. Tissues were also stained with a BPSA-specific monoclonal antibody.

Results:
Total PSA and BPSA were 3-4x more concentrated in TZ than PZ. Nodules and non-nodular tissue had similar PSA and BPSA concentrations. %BPSA in nodule A was correlated with %BPSA in nodule B (r=0.88) and non-nodular TZ tissue (r=0.65), as well as with age (r=0.67), prostate volume (r=0.59), glandular composition (r=0.56), and %BPSA in the PZ (r=0.53). Pre-prostatectomy sera of these patients contained a mean of 8.6, 1.6, and 0.44 ng/ml of PSA, free PSA, and BPSA, respectively. Differential BPSA staining intensity was observed in the three tissues studied (see table).

Conclusions:
BPSA is associated with large prostates containing BPH nodules, being present in both nodular and non-nodular TZ tissue. Localization studies indicated relative concentration of BPSA in TZ nodules. The great concentration of PSA within the TZ indicates the central prostate as the likely origin of serum PSA and BPSA. In these patients, BPSA represented a mean of 25% of the free PSA in the serum. BPSA is a possible biomarker for BPH.

PSA Publications from USRF:

1. Effects of TURP on serum PSA in Men with BPH
2. Identification of BPSA
3. BPSA is a Potential Serum Marker for BPH (2001 AUA Abstract)
4. Identification of proPSA
5. hK2 Is a Cancer-specific Kallikrein in the PSA Family
6. How Does Finasteride Affect Free PSA?