Inactive free : total prostate specific antigen ratios in ejaculate from men with suspected and known prostate cancer, compared with young control men

Abstract

Inactive free : total prostate speci®c antigen ratios in ejaculate from men with suspected and known prostate cancer, compared with young control men Objective To measure free : total prostate speci®c antigen (PSA) ratios in ejaculate from men with suspected and known prostate cancer, and in young control men, to determine if this ratio might be useful in discriminating benign from malignant prostatic conditions. Patients, subjects and methods Forty-seven men with prostate cancer (positive biopsies), 52 men with suspected prostate cancer but who had negative biopsies and 28 young men (<30 years old) and with no family history of cancer, provided either a single ejaculate specimen (total 59) or multiple specimens (total 193) on subsequent occasions. Free and total PSA were measured using appropriate assays. All specimens were diluted in a PSA-negative female serum pool. Results The median free : total PSA ratios were 0.76±0.81 among the patient groups and control men, and there was no statistical difference between the groups. These data presumably only re¯ect the inactive component of free PSA, given that any a 2 -macroglobulin or a 1 -antichymotrypsin in the assay serum diluent was likely to have bound the active free PSA component in these samples. Similar results were obtained from those providing single and multiple samples, suggesting that a single specimen is suf®cient to re¯ect the seminal plasma free : total PSA ratio over that period. There was no relationship between seminal plasma free : total PSA ratio and age for the controls or the positive biopsy group, although there was a negative relationship (i.e. a decline with age) that almost reached signi®cance in those with negative biopsies (P=0.058, R 2 =0.07). Conclusions This is the ®rst report of free : total PSA ratios in the ejaculate of men with suspected and known prostate cancer compared with young control men. Although no signi®cant changes were detected in the free : total PSA ratios in ejaculate, these results may be confounded by differences in ratios with age, as is the case for serum PSA or different molecular forms of PSA. Indeed, these data suggest that a large proportion of free PSA in seminal plasma may be inactive. Further studies are needed to determine the potential utility of measuring free : total PSA, or other candidate markers, in ejaculate to better discriminate benign from malignant prostate disease.

Androgen receptor CAG repeat length correlates with semen PSA levels in adolescence

“…However, measuring serum levels of PSA under normal conditions, i.e., in healthy men is probably not the optimal way of assessing prostate gland function. In men without prostatic disease, the levels of the PSA in seminal fluid is about 106 times higher than in serum [18], the former being the natural way of excretion of this enzyme. Measuring seminal amounts of PSA is thus a better approach to evaluate androgen dependent prostate function.…”

Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients

“…Moreover, SP donation is completely non-invasive avoiding the discomfort and possible concerns associated with prostate massage necessary to obtain post-massage urine. Previously, we reported that the inactive free:total PSA ratios in SP from men with suspected PCa did not distinguish between those harboring malignant as opposed to benign disease [16]. The present study was designed to assess changes in Dkk-3 levels in SP and its potential for discriminating benign from malignant prostatic conditions in patients who were to undergo TRUS-guided biopsy due to elevated serum PSA (> 4 ng/mL) and/or abnormal DRE.…”

“…Samples were layered over 10 mL of 64% isotonic Percoll (Amersham Biosciences) and centrifuged at 2200 rpm for 30 min at 4°C. The ejaculate supernatants (SP) were removed, aliquoted and stored at -70°C until further processing (as reported previously [16,17]). The study had the approval of the ethics committees of the RBWH and University of Queensland.…”

Seminal Fluid Characterization for Male Fertility and Prostate Cancer: Kallikrein-Related Serine Proteases and Whole Proteome Approaches

“…The major seminal fluid protein of prostatic origin is PSA or KLK3 at a concentration of 0.5 to 3.0 mg/mL. [9][10][11][12][13] In contrast to serum, PSA in seminal fluid is predominantly (95%) uncomplexed. 13 The main forms of free PSA (those not complexed; that is, not bound to inhibitors) in seminal fluid include the mature form that is capable of enzymatic activity, and internally clipped or N-terminally truncated forms that are enzymatically inactive.…”

“…19,48 KLK5 can also complex with a 1 -antitrypsin and a 2 -macroglobulin in serum and ascites fluid. 49 In contrast to PSA, all of these proteases ( KLKs 1,2,4,5,6,8,10,11,13,and 14) are trypsin-like, with a preference to cleave protein substrates after an arginine or lysine residue (reviewed by Clements et al, 5 Rittenhouse et al, 13 and Borgono. 50 Because they are secreted as inactive zymogens and most (except for KLK4) require cleavage of their propeptide after lysine (KLK6, 8,13,14) or arginine (KLKs 1, 2, 3, 5, 10, 11), the presence of several different KLK proteases in the seminal fluid suggests that a tightly regulated KLK enzymatic cascade may exist.…”