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RESEARCH ARTICLE
Year : 2003  |  Volume : 19  |  Issue : 2  |  Page : 120-124
 

Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease


1 Department of Biochemistry, Christian Medical College, Ludhiana, India
2 Department of Surgery, Christian Medical College, Ludhiana, India

Correspondence Address:
R Chawla
Department of Biochemistry, Christian Medical College & Hospital, Ludhiana - 141 008
India
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Source of Support: None, Conflict of Interest: None


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   Abstract 

In recent years, prostate specific antigen (PSA) has es­tablished itself as the most useful marker for adenocarci­noma of the prostate and has almost replaced the total acid phosphatase and prostatic acid phosphatase (PAP) for screening, diagnosis and monitoring the prostate car­cinoma patients. The PSA levels also rise in benign hyper­plasia of prostate (BPH) but to a lesser extent and high values are usually diagnostic of malignant disease. The present investigation was conducted to study the relevance of PAP estimation with or without PSA in prostatic dis­ease particularly in the context of hospitalized patients with retention of urine. Levels of the 2 markers were esti­mated in 132 patients with prostatic disease and results correlated with histological findings. BPH was detected in 112 patients whereas 20 patients were diagnosed with adenocarcinoma (ADCA) of prostate. Majority of the pa­tients in our study were referred from private clinics and 66.1 % of BPH and 50% of ADCA patients presented with acute urinary retention. Mean PSA and PAP levels in ad­enocarcinoma group were significantly higher (292.7 and 117.35 ng/ml, respectively) than in BPH group (7.05 and 1.92 ng/ml, respectively). It was observed that PSA levels were raised in BPH patients with urinary retention as com­pared to those with no retention. There was, however, no significant change in PAP levels in these patients. There was a very good correlation between the values of tumor markers (correlation coefficient: 0.86) in all the patients. Therefore, PAP is still a very good tumor marker of prostatic disease with almost comparable efficiency to that of PSA in differentiating the malignant from the benign dis­ease. It appears to be particularly important in hospital­ized patients with acute urinary retention as catheterization appears to raise the levels of PSA but not those of PAP.


Keywords: PSA, PAP, BPH, prostate, catheterization.


How to cite this article:
Chawla R, Abraham R, Arora U, Mammen K. Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease. Indian J Urol 2003;19:120-4

How to cite this URL:
Chawla R, Abraham R, Arora U, Mammen K. Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease. Indian J Urol [serial online] 2003 [cited 2020 Nov 28];19:120-4. Available from: https://www.indianjurol.com/text.asp?2003/19/2/120/37142



   Introduction Top


Benign hyperplasia of prostate (BPH) is a common oc­currence in all men above 60 years of age, whereas its malignant counterpart, carcinoma of prostate, is the lead­ing cause of mortality amongst all the carcinoma in men. Prostatic acid phosphatase (PAP), a sialoglycoprotein with a molecular weight of 100,000 [1] has been used for early screening and detection of prostate carcinoma in high risk group, [2],[3] although its role in staging the carcinoma has been doubtful. [4],[5] Prostate specific antigen (PSA), first iden­tified by the Wang et al, [6] is a 237-amino acid monomeric serine protease, with a molecular weight of 33-34 kilo­daltons. [7] It has shown considerable promise and has been acclaimed the best marker for prostate malignancy in re­cent years, although its plasma concentration also increases in BPH, but to a lesser extent. The reduced specificity of the two markers is further complicated by a number of pathological factors like prostatic infarct, acute bacterial prostatitis as well as acute urinary retention or digital rec­tal examination (DRE). [8],[9]

Since a majority of the prostate patients are referred to the hospital after urinary retention and catheterization, the levels of tumor markers may be falsely elevated in these patients. The present study was planned to see the effect of urinary retention on plasma concentration of PSA and PAP.


   Patients and Methods Top


The serum samples were collected from 132 patients with prostatic disease, who presented at the urology clinic of Christian Medical College Hospital. The sera were stored frozen till analysis for PSA and PAP by radioimmunoassay. The biopsy or the tissue slices collected after transurethral resection of prostate (TURP) were sent to histopathology laboratory for the final diagnosis and the patients were grouped accordingly. A careful clinical examination in­cluding DRE was also performed. On the basis of biopsy reports 112 patients were diagnosed to have benign hyper­trophy (BPH) and 20 patients adenocarcinoma (ADCA) of prostate. Serum PSA and PAP levels were estimated, in the blood samples drawn before digital rectal examina­tion, by immunoradiometric (IRMA) assays using the com­mercial kits supplied by Diagnostic Products Corporation (DPC), USA. The PSA kit is based on ligand-coated tubes and three monoclonal anti-PSA (1 125 I-labelled and 2 lig­and-labelled) antibodies. PSA in patient's serum is cap­tured between the 2 monoclonals. Separation is achieved by ligand-coated tube/anti-ligand bridge method. The kit is designed to measure the total PSA (free PSA as well as the PSA bound to different proteins) in the patient's se­rum. The results were analysed with the help of a compu­ter software (Epi-Info ver 6.0) designed specifically for hospital/epidemiological research work.


   Results Top


The patients in the study ranged from 48 years to 95 years of age with maximum cases belonging to 6th or 7th decades of life. Majority of the patients in both the groups presented with symptoms of urinary obstruction, frequency of micturition, nocturia and hesitancy, whereas in the ADCA group 40% of patients presented with bone pain. About 50% of the ADCA and 67% of BPH patients in our study had urinary retention, signifying the advanced stage of disease in which the patient presented. Since the local stimulation of the prostate is known to influence the levels of the tumor markers, catheterization as well as DRE was performed after the collection of blood samples for PSA and PAP estimation in patients who were not catheterized on admission.

In general, both tumor markers showed significantly (p<0.01) higher concentrations in ADCA patients as com­pared to those with benign disease. All the ADCA patients, except one, had PSA as well as PAP levels elevated above the corresponding normal ranges. The serum PSA was el­evated to greater extent (mean 292.7 ± 65.4 SE ng/ml) than PAP (mean 117.35 ± SE ng/ml) in these patients, whereas the corresponding values for the BPH cases were 7.05 ± 0.77 and 1.92 ± 0.11 ng/ml, respectively [Table - 1]. Within the BPH group, the mean PSA and PAP concentra­tions in patients with urinary retention were 8.59 ± 1.07SE and 1.97 ± 0.14 SE, respectively. The corresponding values for the no-retention cases were 4.07±0.80 SE and 1.85 ± 0.19 SE. The PAP range for BPH group was 0.0 to 5.6 ng/ml compared to ADCA range of 28.0 to 543.9 ng/ ml (excluding 1 patient mentioned above). 1 patient who had slightly elevated PSA (3.7 ng/ml) and normal PAP (1.5 ng/ml) values presented with abnormal DRE. The transrectal ultrasound (TRUS) showed normal homog­enous echotexture and the prostate capsule was intact. The transrectal needle biopsy also proved inconsequential. The histological examination of the prostatic chips resected by TURP revealed the presence of adenocarcinoma of pros­tate.

Amongst the 74 BPH patients with urinary retention, 42 (56.8%) has elevated PSA [Table - 2],[Figure - 1]; 8 (10.8%) of these patients even showed PSA concentrations above 25 ng/ml. In the no-retention subgroup, only 11 out of 38 (28.9%) had above normal (>3.0 ng/ml) PSA concentra­tions and in none of these patients the PSA concentration was more than 25 ng/ml. The proportion of the patients with elevated PAP levels, on the other hand, was almost equal in retention (39.2%) and no-retention cases (44.7%). No patient in either of the groups showed PAP more than 10 ng/ml [Table - 3],[Figure - 1].

There was a good correlation in the values of PSA and PAP in the study [Table - 4]. The PSA values were always higher than PAP with significant overall correlation be­tween the two (r=0.86). When the correlation was analyzed separately in the two groups, the two parameters were re­lated closely (r=0.7 1) in the adenocarcinoma group whereas in BPH group the correlation (r=0.20) was not very good. The correlation coefficient in patients with and without urinary retention (ADCA + BPH) was 0.89 and 0.91, re­spectively. Regression of PSA over PAP [Figure - 2] showed that rise in PSA levels was sharper than that in PAP levels in the urinary retention group.


   Discussion Top


Since the introduction of PSA into clinical use, investi­gators have continuously evaluated its performance as com­pared to PAP. In this study the relative merits of PSA vis a vis PAP in differentiating prostatic carcinoma from hy­perplasia have been compared particularly with reference to the patients with acute urinary retention and catheteri­zation.

There was a significant difference (p=0.0002) in the mean serum PSA levels in the adenocarcinoma patients and the BPH group. The mean PSA (7.05 ng/ml) in BPH group was also above the reference normal range and com­pares well with that reported in literature. [10] Fifteen (75%) of our patients had PSA levels higher than 100 ng/ml and only one patient with intracapsular disease showed nor­mal PSA levels. Saraswati and Malathi [11] working with al­most similar population of patients reported elevated PSA levels in all the 30 pretherapy adenocarcinoma patients.

The mean PAP concentration in adenocacinoma group was also significantly higher than in BPH group. Normal PAP was observed in 1 patient who also had normal PSA levels. The adenocarcinoma patients showed a wider range of elevations (up to 543.9 ng/ml) compared to BPH group where very mild elevations in PAP were observed. The mean PAP (1.9 ng/ml) in BPH group was also slightly above the upper normal limit, i.e., 1.8 ng/ml.

Most of our patients had moderately differentiated ad­enocarcinoma which could be another reason for the higher PSA and PAP values in the ADCA patients. The mean PSA and PAP values at various stages of the disease [Ta­ble 5] are similar to the findings of Stamey and Kabalin. [12],[13] They evaluated PSA and PAP against the clinical stage and found that PSA correlated very well with the clinical stage, whereas PAP was much less discriminating even failing to distinguish extracapsular cancer. In the present study also, the patient with intracapsular disease had nor­mal serum PAP levels (1.5 ng/ml) whereas the PSA levels were 3.7 ng/ml.

Urinary retention was one of the major presenting symp­toms in our study. To study whether urinary retention was 1 of the confounding factors in raising the PSA and PAP levels, the patients in each group were subdivided into those with and without retention. More significant elevation in PSA were observed in patients with than in those without urinary retention. PSA levels as high as 40.6 ng/ml were observed in BPH patients with urinary retention. The PAP estimation on the other hand has proved to he unaffected by this complication as the increase in PAP levels distrib­uted almost equally between the retention and no-reten­tion cases. The mean PAP levels were also identical in the two. The PSA levels are increased in BPH patients pre­senting with urinary retention and values as high as l l 8.2 ng/ml have been reported [9] in such conditions, whereas el­evations in the PAP have also been observed by a few work­ers. [8] The effect of urinary retention in elevations in PSA was further confirmed by significantly high odds ratio (OR) of 3.22 (95% conf. range 1.29 to 8.15). The corresponding OR for PAP was 0.80 (0.33 - 1.87) meaning the increase in PSA is closely associated with urinary retention in BHP patients, whereas PAP levels remain unaffected. There­fore, it appears that PAP is still a good marker for benign prostatic disease in which case it shows very mild altera­tions even in the presence of the complications like uri­nary retention which raise the PSA concentrations to the levels generally representing the cancerous state. This rise in the levels in PSA with urinary retention may be due to the retention pressure and/or physical stimulation by cath­eterization. Oremak and Seiffert studied 301 healthy vol­unteers and reported that physical activity increases the PSA levels by threefolds whereas PAP levels showed mini­mal elevations. Therefore, it appears that the amplitude of elevation of PAP levels in BHP patients is very low com­pared to PSA which suggested different mechanisms for increase in serum PSA and PAP levels. Further, all of the serum PSA might not be of prostatic origin in these cases, because PSA no longer enjoys the 100% tissue specificity acclaimed earlier. [15] The immunoreactive PSA might be contributed by periurethral glands [16] to some extent, par­ticularly in patients with urinary retention.

In the present study, we have observed almost perfect correlation between the values of PSA and PAP [Table - 4]. Surprisingly, a very good correlation between the 2 mark­ers was also found in cases with urinary retention [Figure - 2]. The rest of our data suggested that the PSA is raised in these patients, whereas PAP is unaffected. The high corre­lation coefficient in these patients, however, signifies that long with PSA, PAP is also raised in this condition but the rise in PSA is much sharper than that in PAP. The slope of PSA levels per unit rise in PAP was 2.8. The rise in PAP values by urinary retention and catheterization is too small to affect the average and cut-offs and hence the perform­ance of the assay.

 
   References Top

1.McCarthy RC, Jakubowsky HV. Markowitz H. Human prostatic acid phosphatase: purification characterization and optimisation of condition of radioimmunoassay. Clin Chem. Acta 1983; 132: 287­-92.  Back to cited text no. 1    
2.Cooper VF. The radioimmunochemical measurement of prostatic acid phosphatase: current state of the art. Urol Clin N Am 1980; 7: 653-56.  Back to cited text no. 2    
3.Vinko P. Konturri M. Lukkarinen O. Ervash J, Vinko R. Screening for carcinoma of the prostate, rectal examination and enzymatic and radioimmunologic measurements of serum acid phosphatase compared. Cancer 1985; 56: 173-79.  Back to cited text no. 3    
4.Whitesel JA, Donahue RE, Man: JH et al. Acid phosphatase : its influence on the management of carcinoma of the prostate. J Urol 1984: 131: 70-73.  Back to cited text no. 4    
5.Heller JE. Prostatic acid phosphatase: its current clinical status. J Urol 1987; 137: 1091-1095.  Back to cited text no. 5  [PUBMED]  
6.Wang MC, Valenzuela LA, Murphy GP, Chu TM. Purification of human prostate specific antigen. Invest Urol 1979; 17: 159-163.  Back to cited text no. 6  [PUBMED]  
7.Lilja HA. A kallikrein like serine protease in prostatic fluids cleaves the predominant seminal vesicle protein. J Vlin Invest 1985; 76: 1899-1902.  Back to cited text no. 7    
8.Collier DS, Pain JA. Acute and chronic retention of urine: rel­evance of raised serum prostatic acid phosphatase levels: A pro­spective study. Urol 1986; 27: 34-41.  Back to cited text no. 8  [PUBMED]  
9.Armittage TG, Cooper EH, Newling DWW, Robinson MRG, Appleyard I. The value of the measurement of serum prostatic spe­cific antigen in patients with benign prostatic hyperplasia and un­treated prostatic cancer. Br J Urol 1988; 62: 584-588.  Back to cited text no. 9    
10.Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317: 909-913.  Back to cited text no. 10  [PUBMED]  
11.Saraswati A, Malathi T. A comparative study of tumor markers of adenocarcinoma prostate. Ind J Clin Chem 1995; 10: 29-33.  Back to cited text no. 11    
12.Oremek GM, Seiffert UB. Physical activity releases prostate spe­cific antigen (PSA) from prostate gland into blood and increases serum PSA concentrations. Clin Chem 1996; 42: 691-695.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Stamey TA, Kabalin JN, Femari M, Yang N. Prostate specific anti­gen in the diagnosis and treatment of adenocarcinoma of the pros­tate IV: Antiandrogen-treated patients. J Urol 1989; 141: 1088-1095.  Back to cited text no. 13    
14.Stamey TA, Kabalin JN. Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of prostate I : untreated patients. J Urol 1989; 141: 1070-1075.  Back to cited text no. 14  [PUBMED]  
15.Diamandis EP. Prostate specific antigen - A cancer fighter and a valuable messenger. Clin Chem 2000; 46: 896-900.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Diamandis EP, Yu H. Non-prostatic sources of prostate specific an­tigen. Urol Clin N Am 1997; 24(2): 275-81.  Back to cited text no. 16    


    Figures

  [Figure - 1], [Figure - 2]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]

This article has been cited by
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Kathmandu University Medical Journal. 2010; 8(30): 158-163
[Pubmed]



 

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    Abstract
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