Paper

Prostate Cancer and Prostatic Diseases (2003) 6, 163–168. doi:10.1038/sj.pcan.4500649

cPSA and fPSA elimination in African-American men

B J Martin1, C Cheli2, R Davis3, M Ward1, M Kokatnur1, D Mercante1, D Lifsey1 and W Rayford1

  1. 1Department of Urology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
  2. 2Bayer Corporation, Tarrytown, New York, USA
  3. 3Tulane University, New Orleans, Louisiana, USA

Correspondence: Dr W Rayford, Louisiana State University Health Sciences Center, Department of Urology, 1542 Tulane Avenue, Room 534, New Orleans, LA 70112, USA. E-mail: wrayfo@lsuhsc.edu

Received 9 October 2002; Accepted 12 June 2002.

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Abstract

In all, 22 African-American males undergoing radical prostatectomy for prostate adenocarcinoma had serum drawn for tPSA, cPSA, and total protein concentrations prior to, during, and after operation to determine the respective elimination rates. African-American cPSA was found to fit best a simple first-order exponential elimination kinetic, with a half-life of 44.6 h. fPSA followed a two-compartment elimination with an alpha-phase elimination of 0.50 h and a beta-phase half-life of 4.2 h. Our results suggest higher rates of elimination for both cPSA and fPSA in an African-American male population with respect to Caucasians and may account for differences in PSA values between races.

Keywords:

African-American, prostate cancer, complexed PSA, kinetics

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Introduction

Measurement of serum prostate-specific antigen (PSA) has been the single most important advancement in the detection of early stage prostate cancer (CaP) in the past 15 y. Since Stamey's proposal for PSA to be used over other tumor markers,1 the incidence of CaP has risen much more dramatically than the mortality rate.2 Based on the Cancer Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute,3 researchers realized that African-American males had a much higher incidence and mortality from prostate cancer than any other ethnic group. While African-American males had a 31% higher detection of prostatic adenocarcinoma than Caucasian males, their mortality rate was an astonishing 117% higher.2,3,4,5

Investigators then began to look for answers to explain these disparate numbers. A number of studies have found that PSA levels in African-American males both with and without cancer are higher than their Caucasian counterparts.4,6,7,8,9,10,11,12 This has led to theories questioning whether the biology of prostate cancer in African-Americans is the same as for Caucasians. African-American males may have a higher tumor burden at diagnosis,6,8 a higher histologic grade,2,6 and more seminal vesicle involvement.7 While these facts could be attributable to socioeconomic factors unique to the United States, leading to a delay in diagnosis,6,13 other clues exist suggesting otherwise. Young African-American men have been shown to have higher average testosterone levels.6 The androgen receptor gene in African-American men may have a lower number of CAG repeats, which has been correlated with a higher risk of cancer of the prostate.6 Montie and Pienta13 have proffered an alternate model of carcinogenesis in African-American males. Based on the finding of increased PIN in African-American males as early as the age of 40 y,14 higher grade tumors may develop earlier. In the setting of an altered hormonal milieu, these cancers could progress faster and present at a higher stage.

In this study, we sought to examine the behavior of PSA and its component fractions, complexed (cPSA) and free (fPSA), in African-American males. We reasoned that differences in the metabolism or elimination of PSA isoforms could contribute to the higher PSA values found among African-American men. Moreover, the rate of production of PSA may be inferred by the rate of elimination, which may give further insight into the activity of prostate cancer in African-American males. At the very least, discrepancies in PSA decay may affect treatment algorithms previously validated for Caucasian men only.

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Methods

Informed consent to participate in this institutional review board-approved study was obtained from 35 consecutive men undergoing radical retropubic prostatectomy for localized adenocarcinoma of the prostate between 1999 and 2001. Blood samples were drawn at the beginning of the surgery (prior to Foley catheter insertion) and again immediately after the prostate gland was removed from the patient. This second blood draw was taken to be time zero (t0) for purposes of kinetics modeling. Samples were then taken postoperatively at 1, 2, 4, 6, 12, 24, 48, and 72 h.

All blood samples were collected in EDTA-prepared tubes and centrifuged to separate the serum. The EDTA serum was then immediately frozen at -80°C and thawed just before analysis. For each sample, cPSA was measured with the Bayer Immuno 1TMcPSA assay (Bayer Corp., Tarrytown, NY, USA), a commercially available monoclonal assay. The assay detects PSA complexed to several protease inhibitors by using an excess of antibody to fPSA, rendering it unavailable for reaction in the cPSA assay.15 tPSA was also measured via the Bayer Immuno 1 technique. fPSA was then calculated as the difference between tPSA and cPSA, based on prior work validating that cPSA plus fPSA was within 5% of the measured tPSA.15 Determination of the serum protein concentration at each blood draw was also performed.

Three models of pharmacokinetic elimination were tested for both cPSA and fPSA using a mathematical modeling program, MLAB (Civilized Software, Bethesda, MD, USA). Curve fitting to the data was performed by the Marquardt–Levenberg method in MLAB. For the following examples, PSA(t) represents the cPSA or fPSA concentration at time t; P0 represents the initial PSA concentration; m, k, alpha, and beta are the rate constants to be solved; and A, B, and C are constants.

The simplest model of elimination of a substance from the blood stream is by a linear relationship, where a constant amount of a substance is eliminated per unit time. Equation (1) depicts this situation below:

Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Next, a simple first-order exponential elimination was evaluated, of the form

Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

In this model, a constant fraction of a substance is eliminated per unit time. The amount of time necessary for one-half of the substance to be cleared from the circulation is expressed as the half-life (t1/2), calculated as the natural logarithm of two divided by the rate constant, k. Often in the body, however, a substance must first equilibrate between the vascular space and some other volume of distribution, such as the interstitial space or the intracellular space. This two-compartment model can be constructed mathematically as a combination of two individual exponential functions, as follows:

Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

The first term in the equation represents the initial equilibration and the second term represents the eventual clearance of the substance from the serum. A half-life can then be calculated for each of these phases of elimination.

Each patient was individually processed through each model for both cPSA and fPSA, with objective 'tightness of fit' estimated by the determination coefficient, R2. Also, a graphical depiction of the data and each function generated was visually inspected to ensure correct correlation. Statistical analyses were then performed on the resultant rate coefficients and calculated half-lives to determine trends in PSA elimination based on preoperative PSA level, pathologic stage, and grade.

Additionally, an attempt was made to correct for the hemodilutional effects of surgery, as previous authors have suggested that the early phase of PSA elimination is influenced by the fluid shifts inherent in major surgery.16 If one assumes a constant intravascular volume, a drop in the serum protein concentration postoperatively could reflect dilutional effects, and the true concentration of other blood-borne substances would be in effect higher. While the actual blood volume undoubtedly does fluctuate, this simple assumption allows us to construct a model relating relative hemodilution to the PSA concentration. Mathematically, this could be expressed as below:

Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

where [prot]init is the preoperative total serum protein value, and [prot]t is the measured protein at the given time point. cPSA* and fPSA* were therefore calculated as above for each patient at each time point and subjected to the same models as described above.

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Results

Of the 35 patients enrolled, 22 were included in this study. Two patients were excluded due to Caucasian race, one patient was excluded due to preoperative LHRH-agonist therapy, and 10 patients because of insufficient blood sample collection. Patient demographics are presented in Table 1. The average patient was 60.3 y old with a cPSA of 7.46 ng/ml and a fPSA level at 2.01 ng/ml. In all, 16 had pathologically organ-confined disease. Only six patients had positive margins, and one patient had a single lymph node involved with tumor. No patient was found to have detectable PSA at the 30-day postoperative visit, suggesting metabolically insignificant residual disease. Average blood loss was less than 1 l, with only two patients requiring the transfusion of blood products.


Of the 22 patients, 19 experienced a rapid rise in fPSA from the preoperative level to time zero, specimen excision. Only 13 saw an elevation of the cPSA level from baseline, with three of these patients not reaching a peak cPSA concentration until 4 or 6 h postexcision.

For the following models, tightness of fit was arbitrarily defined as an R2 determination coefficient greater than 0.700 and visual confirmation of appropriate fit on a graphical representation of the resultant function.

Linear kinetics

Of the 22 patients, 17 showed a good fit for cPSA to a linear model of elimination. The average slope of decay was 0.076 ng/ml/h. Using cPSA*, the cPSA value adjusted for protein loss by Equation (4), 19 out of 22 had an appropriate fit to the linear model, with 72% of the patients found to have higher R2 values than with cPSA alone. The average slope for cPSA* was 0.103 ng/ml/h. No linear model could be constructed for fPSA or fPSA*.

First-order kinetics

Again, 17 out of 22 showed a good fit to the simple exponential model presented in Equation (2). The average decay coefficient for cPSA was 0.0156/h, yielding a cPSA half-life of 44.6 h (range 16.8–123.5 h). Overall, curve fitting to this model was superior to the linear plot, with greater R2 values for most patients. Using cPSA* values, an even tighter fit was achieved, with 19 out of 22 displaying an R2 value greater than 0.850. For 16 out of the 22, this was an improvement in fit. The average decay coefficient for cPSA* was higher at 0.0199/h, with a cPSA* half-life of 34.9 h (range 13.6–84.5 h).

fPSA fit well to an exponential model, with 86% (19 out of 22) meeting the criteria for tightness of fit. The average decay coefficient was 0.577/h, resulting in an average half-life of 1.20 h (range 0.36–42.0 h). The adjusted fPSA* showed marked improvement in curve-fitting, with 19 out of 22 enhanced by the transformation, yielding 20 out of 22 with R2 coefficients greater than 0.700. The fPSA* mean elimination occurred at a rate of 0.566/h, with a half-life of 1.22 h (range 0.34–29.1 h).

Two-compartment first-order kinetics

No model could be fashioned to fit cPSA or cPSA* to a two-compartment model. fPSA, however, displayed exceptional curve-fitting to this kinetic. Of the 22, 17 had R2 values greater than 0.900 (an additional patient fit well with R2=0.77). The average early phase, or alpha-phase, elimination showed a half-life of 0.50 h, with a late, or beta-phase half-life of 4.20 h. Visually, the curve fitting for the two-compartment model was far superior to the simple first-order model.

The same number of patients fit well to the fPSA* model (18 out of 22), but in 13 out of 22 the R2 values were higher, supporting better curve-fitting when accounting for hemodilution. For this model, the alpha-phase half-life was 0.87 h with a beta-phase elimination of 5.51 h.

Figure 1 shows a representative patient's plotting of cPSA and fPSA data to the above models. The illustration also shows curve-fitting to cPSA* and fPSA* data for comparison.

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Graph of PSA elimination for one representative patient. X-axis denotes time after prostate removal, in hours. Y-axis is PSA concentration, in ng/ml. Red data points and lines plot raw PSA data; blue points and lines reflect transformed PSA* data. (a) Linear kinetics of cPSA and cPSA*. (b) First-order exponential kinetics of cPSA and cPSA*. (c) First order kinetics of fPSA and fPSA*. (d) Two-compartment model of fPSA and fPSA*.

Full figure and legend (73K)

Statistical analyses

Next, we examined whether clinical or pathologic parameters influenced the observed elimination rates. Preoperative tPSA (less than 10 ng/ml), pathologic stage (less than T2c), Gleason sum (2–4, 5–6, or 7–10), or margin status (negative or positive) were all evaluated for statistically significant differences in rates of elimination. The data were found not to be normally distributed by the Shapiro–Wilk test; therefore, nonparametric tests for the equality of medians were used (either the Wilcoxon or Kruskal–Wallis test, as appropriate).

Only negative margin status in the beta-phase elimination of fPSA was determined to have a statistically significant lower half-life (3.1 h vs 27.5 h for positive margins, P=0.006). Patients with negative margins had an average cPSA half-life of 40.3 hours, while those with positive margins averaged 58.2 h, but this was not statistically significant (P=0.27). Preoperative tPSA, Gleason grade, and pathologic stage were not predictive of faster rates of elimination for complexed or free PSA (data not shown).

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Discussion

PSA is a neutral serine protease produced almost exclusively by prostatic epithelial cells. The majority of PSA in serum exists as a complex with various protease inhibitors, the most important of which is alpha-1-antichymotrypsin (ACT).15 The Bayer Immuno 1 Assay (Tarrytown, NY, USA) for PSA uses the MM1 monoclonal antibody to detect both free and complexed forms of PSA. With the addition of an excess of the ME2 antibody, which binds the free PSA alphaE-epitope, the free portion of PSA is eliminated from reaction with MM1, and the resulting measurement is representative of the cPSA fraction.15 While fPSA has a molecular weight of approximately 37 kDa, the various PSA complexes have molecular weights between 78 kDa (for PSA-alpha2-macroglobulin) to 100 kDa (PSA-ACT).17 This would suggest either that the body eliminates these substances by different mechanisms or that the free portion must bind to a protease inhibitor before metabolism.

Various authors have suggested that fPSA, of similar weight to albumin, is excreted by the kidney.17,18,19 cPSA, however, is too large for glomerular filtration; in fact, Semjonow et al,20 failed to detect total PSA in the urine following radical prostatectomy. Receptors for serpin–enzyme complexes have been discovered on the surface of hepatocytes,21,22 suggesting hepatic metabolism of PSA complexes. Agha et al,17 measured a significant concentration drop of total PSA through the hepatic circulation, supporting this theory.

Few studies exist, however, examining strictly the elimination rate of cPSA. Stephan et al,23,24 found very stable levels of cPSA for the first 6 h after surgery, followed by a steady decline. Therefore, these authors were unable to calculate an elimination rate with a two-compartment model. Likewise, Lilja et al,19 commented that cPSA elimination seemed to follow a linear, zero-order kinetic, but were unable to calculate a value because of insufficient sample size. Bjork et al,25 studied 10 patients and found the linear elimination to be 0.8 ng/ml/day.

In African-American men, we found that cPSA best fits an exponential model. However, we did achieve a reasonable fit for 17 of our 22 patients to a zero-order model. The average elimination rate was 0.076 ng/ml/h, or 1.8 ng/ml/day, much greater than that published by Bjork.

For comparison of our cPSA elimination rates, then, we must turn to prior studies with tPSA. Table 2 summarizes these reports. Presumably, these studies were performed primarily on Caucasian patients, and there is disagreement on the best model for elimination. For those supporting a first-order elimination, half-lives range from 45.6 to 75.6 h.20,26,27 For those espousing a two-compartment model, the beta-phase half-lives range from 33 to 182 h.1,16,24,26,28 It is possible that the two-compartment models with tPSA truly reflect an alpha-phase elimination of fPSA and the beta-phase represents the first-order elimination of cPSA.


Our finding of an African-American male cPSA elimination half-life of 44.6 h falls within the lower range of these studies. This may suggest that African-American male elimination of cPSA is faster than for Caucasian men.

Multiple studies do exist, however, looking at the elimination of fPSA from serum (see Table 3). There is universal agreement that fPSA follows a two-compartment model of elimination, with the alpha-phase ranging from 0.57 to 1.8 h, and the beta-phase half-life lasting 6.0–22 h.16,18,19,24,25,28 Our results agree with this two-phase pattern of elimination, but our calculated half-lives appear to be much shorter than those previously published, with an initial half-life of 0.50 h and a later half-life of 4.20 h. Again, this suggests African-American men eliminate fPSA faster than Caucasian men.


There are currently three theories to explain the two-compartment model of fPSA elimination. The first theory asserts that fPSA is rapidly excreted by the kidneys, consistent with its low molecular weight, which accounts for its faster, initial phase elimination.18,19,28 A second theory states that fPSA forms complexes in the serum with protease-inhibitors, thus rendering it undetectable by fPSA assay methods but not truly removing it from circulation.23,29 Stephan et al,24 lent support to this theory by demonstrating constant levels of cPSA while fPSA levels dropped in the immediate postoperative period. The final theory states that the initial phase merely reflects perioperative hemodynamic changes and fluid shifts, so that the true elimination of fPSA does not manifest until the prolonged, later beta-phase.1,16,25 Brandle et al,16 found that serum protein and albumin concentrations demonstrated statistically similar rates of decay to fPSA and tPSA in the immediate postoperative period, suggesting that the alpha-phase was an artifact.

To test this final theory, we attempted to account for changes in PSA concentrations commensurate with changes in the serum total protein concentration. We used a simple mathematical transformation (Equation (4)) based on the idea that if serum protein concentrations dropped, this signified hemodilution, and the true PSA concentrations would be higher were it not for this effect. Support for this notion comes from the fact that the intraoperative fluid replacement was much greater than the estimated blood loss for all patients (see Table 1). For the majority of patients, serum protein values fell immediately after the operation but returned to baseline levels by 6–48 h postoperation. Therefore, our transformation of PSA values had the maximum effect during the initial alpha-phase in question.

These mathematically transformed PSA values, called cPSA* and fPSA*, actually demonstrated superior curve-fitting for all models of elimination (see Figure 1). The calculated half-life for cPSA* was 34.9 h. fPSA* displayed an initial half-life of 0.87 h, and a beta-phase elimination half-life of 5.5 h. As before, these values are well below previously reported elimination rates of tPSA or fPSA in Caucasian men. Additionally, this crude manipulation of the concentrations suggests that while perioperative fluid changes may affect our observed elimination of fPSA, it cannot be responsible for the entire early phase seen. Also, if postoperative factors were the major influence on cPSA or fPSA elimination in the first few hours, then both would follow a two-compartment model, which was not seen in our study.

From all of the above results, the rate of elimination of both cPSA and fPSA in African-American men appears to be faster than previously published rates for Caucasian men. At steady-state conditions, the rate of PSA elimination from the circulation should equal the rate of PSA entrance into the circulation. Increased amounts of PSA in the circulation would result from either increased rates of PSA production by the carcinoma or faster rates of diffusion into the vascular space by PSA. Therefore, our elimination rates suggest either that both fPSA and cPSA production in African-American men exceed that of Caucasian men, or that there is greater communication between the tumor cells and the blood stream in African-Americans. This could lend further support to the theory that prostate cancer in African-American men is biologically distinct from that of Caucasian men.

We next explored whether the tumor pathology exerted an influence on the elimination half-lives for cPSA and fPSA. In general, no statistically significant difference was seen based on tPSA, Gleason sum, pathologic stage, or margin status. Only the delayed excretion phase of fPSA showed a shorter half-life in margin-negative patients (3.1 vs 27.5 h). Semjonow et al,20 however, found longer half-lives for tPSA in patients shown to have a biochemical failure at follow-up. Six of our patients had positive margins at surgery, but none had detectable PSA levels at his 1 month postoperative visit. Longer follow-up for our patients will be necessary to prove that cancer persistence or recurrence was not responsible for the lengthened half-lives.

If those patients most likely to have biochemical failure because of microscopic tumor foci persistence after surgery, that is, those with positive margin status, are excluded from the analysis, the elimination half-lives for African-American males become even lower. The average cPSA elimination half-life for margin-negative patients was 40.3 h. For fPSA, the alpha-phase half-life was 0.41 h with the delayed beta-half-life only 3.1 h. Again, these values suggest higher baseline free- and complexed-PSA production rates or vascular diffusion rates in African-American males at steady state.

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Conclusions

The elimination of cPSA from serum in African-American men follows a simple first-order kinetic with a half-life of 44.6 h. Considering only patients with negative margins, this half-life falls to 40.3 h, while adjusting for hemodilutional effects of surgery lowers the elimination half-life further to 34.9 h. The elimination of fPSA follows a two-compartment model, with an initial alpha-phase half-life of 0.50 h and a later beta-phase half-life of 4.2 h. Patients with negative operative margins showed faster elimination rates of 0.41 h for the alpha-phase and 3.1 h for the beta-phase. These values may be increased slightly to 0.87 and 5.5 h, respectively, if hemodynamic factors are included. These are the first reports of cPSA and fPSA elimination in African-Americans. Further work is needed in the pharmacokinetics of cPSA and fPSA in both Caucasian and African-American men to determine if there are fundamental biochemical differences in the behavior of PSA between the two races. The work aimed at quantifying PSA production in vivo may also validate our findings.

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References

  1. Stamey TA et al. Prostate specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317: 909–916. | PubMed | ISI | ChemPort |
  2. Brawley OW, Knopf K, Merrill R. The epidemiology of prostate cancer Part I: descriptive epidemiology. Sem Urol Oncol 1998; 16: 187–192.
  3. Miller BA et al. Cancer Statistics Review: 1973–1989. National Cancer Institute: Bethesda, MA, 1992.
  4. Smith DS, Bullock AD, Catalona WJ, Herschman JD. Racial differences in a prostate cancer screening study. J Urol 1996; 156: 1366–1369. | Article | PubMed |
  5. Brawley OW. Prostate cancer and Black men. Semin Urol Oncol 1998; 16: 184–186.
  6. Abdalla I, Ray P, Vijayakumar S. Race and serum prostate specific antigen levels: current status and future directions. Semin Urol Oncol 1998; 16: 207–213. | PubMed | ChemPort |
  7. Pettaway CA et al. Prostate specific antigen and pathological features of prostate cancer in Black and White patients: a comparative study based on radical prostatectomy specimens. J Urol 1998; 160: 437–442. | PubMed |
  8. Moul JW et al. Prostate-specific antigen values at the time of prostate cancer diagnosis in African-American men. JAMA 1995; 274: 1277–1281. | PubMed |
  9. Vijayakumar S et al. Racial differences in prostate-specific antigen levels in patients with local-regional prostate cancer. Cancer Epidemiol, Biomarkers Preven 1992; 1: 541–545.
  10. Eastham JA et al. Racial variation in prostate specific antigen in a large cohort of men without prostate cancer. J Louisiana State Med Soc 2001; 153: 184–189.
  11. DeAntoni EP et al. Age- and race-specific reference ranges for prostate specific antigen from a large community-based study. Urolog 1996; 48: 234–239.
  12. Morgan TO et al. Age-specific reference ranges for serum prostate-specific antigen in Black men. N Engl J Med 1996; 335: 304–310. | Article | PubMed | ISI | ChemPort |
  13. Montie JE, Pienta KJ. A unifying model to explain the increased incidence and higher mortality of prostate cancer in Black men. Urology 1999; 53: 1073–1076.
  14. Sakr WA, Grignon DJ, Haas GP. Pathology of pre-malignant lesions and carcinoma of the prostate in African-American men. Semin Urol Oncol 1998; 16: 214–220. | PubMed | ChemPort |
  15. Allard WJ, Zhou Z, Yeung KK. Novel immunoassay for the measurement of complexed prostate specific antigen in serum. Clini Chem 1998; 44: 1216–1223.
  16. Brandle E, Hautmann O, Bachen M. Serum half-life determination of free and total prostate-specific antigen following radical prostatectomy—a critical assessment. Urology 1999; 53: 722–730.
  17. Agha AH, Schechter E, Roy J, Culkin DJ. Prostate specific antigen is metabolized in the liver. J Urol 1996; 155: 1332–1335. | PubMed |
  18. Richardson TD, Wojno KJ, Liang LW. Half-life determination of serum free prostate-specific antigen following radical retropubic prostatectomy. Urology 1996; 48: 40–44. | Article | PubMed | ChemPort |
  19. Lilja H, Haese A, Bjork T. Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular Kallikrein 2 in clinically localized cancer before and after radical prostatectomy. J Urol 1999; 162: 2029–2035.
  20. Semjonow A, Hamm M, Rathert P. Elimination kinetics of prostate-specific antigen serum and urine. Int J Biol Markers 1994; 9: 15–20.
  21. Perlmutter DH et al. Identification of a serpine enzyme complex receptor on human hepatoma cells and human monocytes. Proc Natl Acad Sci USA 1990; 87: 3753–3757. | PubMed | ChemPort |
  22. Mast AE, Enghild JJ, Pizzo SV, Salvesen G. Analysis of the plasma elimination kinetics and conformational stabilities of native, proteinase-complexed, and reactive site cleaved serpins: comparison of alpha1-proteinase inhibitor, alpha1-antichymotrypsin, antithrombin III, alpha2-antiplasmin, angiotensinogen, and ovalbumin. Biochemistry 1991; 30: 1723–1730. | Article | PubMed | ISI | ChemPort |
  23. Stephan C et al. Elimination of serum complexed prostate specific antigen after radical retropubic prostatectomy. Clin Chem Lab Med 2000; 38: 309–311.
  24. Stephan C et al. ACT-PSA and complexed PSA elimination kinetics in serum after radical retropubic prostatectomy: proof of new complex forming of PSA after release into circulation. Urology 2000; 55: 560–563. | Article | PubMed |
  25. Bjork T, Ljungberg B, Pironen T. Rapid exponential elimination of free prostate-specific antigen contrasts the slow, capacity-limited elimination of PSA complexed to alpha1-antichymotrypsin from serum. Urology 1998; 51: 57–62. | Article | PubMed |
  26. Haab F, Meulemans A, Bocon-Gibod L. Clearance of serum PSA after open surgery for benign prostatic hypertrophy, radical cystectomy, and radical prostatectomy. The Prostate 1995; 26: 334–338.
  27. Oesterling JE, Chan DW, Epstein JI. Prostate specific antigen in the preoperative and postoperative evaluation of localized prostatic cancer treated with radical prostatectomy. J Urol 1998; 139: 766–772.
  28. Partin AW, Piantadosi S, Subong ENP. Clearance rate of serum free and total PSA following radical retropubic prostatectomy. The Prostate 1996; 7(Suppl): 35–39.
  29. Colar CB, Coptcoat MJ, Mulvin D. The release of free prostate specific antigen into the circulation during transurethral resection of the prostate: kinetics and interaction with serum protease inhibitors. Br J Urol 1998; 81: 105–108. | PubMed |
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Acknowledgements

We thank Dr Gary Knott for his help with utilization of the MLAB software.

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