Sd. Mikolajczyk et al., A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue, CANCER RES, 60(3), 2000, pp. 756-759
Prostate-specific antigen (PSA) is a widely used serum marker for prostate
cancer (PCa), but in the critical diagnostic range of 4-10 ng/ml it has lim
ited specificity for distinguishing early PCa from benign prostatic hyperpl
asia (BPH), PSA in serum is comprised of a variety of both "free" and "comp
lexed" forms that have been used to improve the specificity of PSA for pros
tate cancer detection. We previously reported that pro PSA (pPSA), the zymo
gen or precursor form of PSA, is a component of free PSA in the serum of PC
a patients. In the current study, we examined prostate tissues to understan
d the origin and specificity of pPSA, PSA was immune-affinity purified from
matched sets of prostate tissues including peripheral zone cancer (PZ-C);
peripheral zone noncancer; and benign tissue from the transition zone (TZ),
the primary site of BPH within the prostate,We found that pPSA is differen
tially elevated in PZ-C, but is largely undetectable in TZ, N-terminal sequ
encing revealed that the pPSA was comprised primarily of [-2]pPSA and minor
levels of [-4]pPSA, containing pro leader peptides of 2 and 4 amino acids,
respectively. The median value of pPSA was 3% in PZ-C and 0% (undetectable
) in TZ (P < 0.0026), No pPSA was detected in 13 of 18 transition zone spec
imens (72%), but only 2 of the 18 matched cancer specimens (11%) contained
no measurable pPSA, These results demonstrate that pPSA is more highly corr
elated with prostate cancer than with BPH, The pPSA in serum may represent
a more cancer-specific form of PSA that could help distinguish prostate can
cer from BPH.