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.
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
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).
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.
Total PSA (µg/mg protein)
BPSA (µg/mg protein)
BPSA Staining Intensity (IHC)
|BPH nodules, TZ
|Non-nodular tissue, TZ
PSA Publications from USRF:
- Effects of TURP on
serum PSA in Men with BPH
- BPSA is
a Potential Serum Marker for BPH (2001 AUA Abstract)
Is a Cancer-specific Kallikrein in the PSA Family
Does Finasteride Affect Free PSA?