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OJHAS: Vol. 3, Issue
3: (2004 Jul-Sep) |
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| The Study Of Serum Prostate Specific
Antigen And Phosphatase Isoenzymes Activity As Diagnostic Parameters In Patients With
Prostate Cancer In Nigeria |
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Igwe
CU
Department
of Medical Laboratory Sciences, Faculty of Pathological Sciences, College Of Medicine,
Ambrose Alli University, Ekpoma
Ikaraoha
CI
Department
of Medical Laboratory Sciences, Faculty of Pathological Sciences, College Of Medicine,
Ambrose Alli University, Ekpoma
Ogunlewe
JO
Department
of Chemical Pathology, Lagos State University Teaching Hospital, Lagos, Nigeria.
Nwobu
GO
Department
of Medical Laboratory Sciences, Faculty of Pathological Sciences, College Of Medicine,
Ambrose Alli University, Ekpoma
Duru
LAD
Department
of Chemical Pathology, Faculty of Pathological Sciences, College Of Medicine, Ambrose Alli
University, Ekpoma-Nigeria
Mokogwu
ATH
Department
of Medical Laboratory Sciences, Faculty of Pathological Sciences, College Of Medicine,
Ambrose Alli University, Ekpoma
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Address For Correspondence |
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Igwe, Chidi U,
Department of Medical Laboratory Sciences,
Faculty of Pathological Sciences,
College of Medicine, Ambrose Alli University,
P.M.B 14, Ekpoma, Edo State, Nigeria.
E-mail: igwechidi@yahoo.com |
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| Igwe CU, Ikaraoha CI,
Ogunlewe JO, Nwobu GO, Duru LAD, Mokogwu ATH. The Study Of Serum Prostate Specific Antigen
And Phosphatase Isoenzymes Activity As Diagnostic Parameters In Patients With Prostate
Cancer In Nigeria
Online J Health Allied Scs.2004;3:3 |
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Submitted: Apr 1,
2004; Accepted: Sep 22, 2004; Published:
Oct 18,
2004 |
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| Abstract: |
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Serum activities of Acid Phosphatase (ACP)
and Prostatic Acid Phosphatase (PAP) are still employed in most hospitals in Nigeria for
the diagnosis of prostate cancer, because of lack of resources for prostate specific
antigen (PSA) assay. Serum PSA and activities of phosphatase isoenzymes ACP and PAP,
Alkaline Phosphatase (ALP) and Heat stable Alkaline Phosphatase (HSAP) were studied in 71
apparently healthy male controls and 47 proven prostate cancer patients. There were
statistically significant increases in the mean serum levels of PSA, PAP, ACP, ALP and
HSAP in the prostate cancer patients compared to the controls (P<0.001). PSA level was
increased above the cut-off level in 85.1% of patients, PAP in 66.0%, ACP in 57.5%, ALP in
34.0% and HSAP in 21.3% of cases. Serum levels of PSA, ACP and PAP were lower and of ALP
and HSAP higher in patients with longer duration of the disease (P<0.05). The study
confirms the relevance of PSA assay over ACP, PAP, ALP and HSAP in the diagnosis of
prostate cancer patients. It highlights the need for the inclusion of PSA assay in
hospitals for accurate diagnosis of prostatic carcinoma.
Key Words:
Prostate Cancer, Prostate specific antigen, Acid phosphatase, Nigeria
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Prostate cancer is the most common malignant tumour in men
over the age of 65 years. It has been declared a public health epidemic in black American
men because of its high incidence.1 Africa was reported in the past to have a
low incidence of this disease,2 however recent studies indicate a high and
rising incidence in Nigerians.3,4
The measurement of acid phosphatase(ACP) isoenzymes is
recommended as a routine screening test for patients whose serum ACP is abnormally high.
This is because the isoenzyme study not only indicates the presence or absence of prostate
cancer but also whether or not there is bony metastasis.5 However, with the
advent of prostate specific antigen (PSA) measurement, assay of ACP and prostatic acid
phosphatase (PAP) in the diagnosis, staging and monitoring of prostate cancer has taken a
back-stage.6 ACP and PAP estimations are still employed in most hospitals in
Nigeria because of lack of resources for PSA.7 On the other hand, heat stable
alkaline phosphatase (HSAP), a placenta – type ALP that is expressed in gonadal and
urologic cancers8, including prostate carcinoma and metastatic diseases with
bony lesions,9 may play a role in the diagnosis of prostate cancer in the
absence of facilities for PSA. Thus, the need for the evaluation and reappraisal of the
combined serum activities of ALP, HSAP, ACP and PAP in the presence or absence of PSA
assay in the diagnosis and monitoring of prostate cancer in Nigeria. This may provide a
simpler, more common and affordable combined method for the diagnosis of this disease
and/or encourage hospital management to improve on the resources necessary for this
diagnosis.
Forty-seven (47) prostate cancer patients
within the ages of 50-90 years were selected from University of Benin Teaching Hospital,
Benin City (UBTH), and Nnamdi Azikiwe University Teaching Hospital, Awka (NAUTH), Nigeria
between July 2002 and July 2003. Prostate cancer patients were grouped as <1 year, 1-2
years and >2 years after diagnosis. The control population was made up of 71 male
volunteers, who were apparently healthy and prostate cancer asymptomatic. They were
selected to match the patients in age and socio-economic status. Informed consent was
obtained from all subjects.
Collection of Samples
Five millilitres (5ml) of venous blood was
obtained from each of the subjects, dispensed into plain container without anticoagulant,
allowed to clot and retract. The serum was separated from the whole blood after
centrifugation and stored frozen until the assay. However, sera for ACP and PAP
estimations were stabilised using 5mg sodium hydrogen sulphate monohydrate per ml of serum
before freezing.
Methods
Serum ALP and HSAP activities were determined using the methods of King and Armstrong,10
and Moss and Whitby11 respectively, employing reagent kits supplied by Randox
Laboratories Ltd, UK. Total ACP and PAP activities were determined using King and Kind
Method12 with reagent kits supplied by Randox Laboratories Ltd, UK. PSA was
determined by the use of AxSYM PSA (Abbott Diagnostics) automated microparticle enzyme
immunoassay technique.13
Statistical Analysis
Statistical methods included student’s two – tailed test for unpaired data and
analysis of variance (ANOVA) for continuous variables. These were carried out with SAS
software (SAS Institute Inc. Cary, North Carolina). The 5% (P<0.05) level of
significance was adopted for significant findings.
The distribution of prostate cancer patients with serum biochemical
values above the cutoff points for the various parameters is shown in Table 1. PSA showed
higher reliability as tumour marker (85.1%), followed by PAP (66.0%), ACP (57.5%), ALP
(34.0%) and HSAP (21.3%).
Table 1: Distribution of patients with biochemical values above the cut-off
(upper-limit of normal)14,15
Parameter |
Number of Patients (%) |
Cut-off point |
PSA (ng/ml) |
40 (85.1) |
4 |
ACP (U/L) |
27 (57.5) |
5.5 |
PAP (U/L) |
31 (66.0) |
1.0 |
ALP (U/L) |
16 (34.0) |
130 |
HSAP (U/L) |
10 (21.3) |
0.0 |
Serum PSA concentration as well as the
activities of ACP, PAP, ALP and HSAP were significantly increased in the prostate cancer
patients compared with controls (P<0.001; Table 2).
Table 2: Serum biochemical values in prostate cancer patients and controls
Parameter |
Patients (n = 47) |
Controls (n = 71) |
P value |
PSA (ng/ml) |
10.6 ± 4.4 |
2.2 ± 0.8 |
<0.001 |
ACP (U/L) |
64.2 ± 35.4 |
7.96 ± 3.4 |
<0.001 |
PAP (U/L) |
59.3 ± 34.5 |
2.6 ± 2.2 |
<0.001 |
ALP (U/L) |
251.7 ± 61.2 |
133.3 ± 55.0 |
<0.001 |
HSAP (U/L) |
2.0 ± 1.6 |
0.13 ± 0.09 |
<0.001 |
| Values
are mean ± SD |
Table 3 shows the comparison of each
parameter in prostate cancer subjects with respect to duration from date of diagnosis. The
serum PSA, ACP and PAP levels were significantly lower (P<0.01) in patients with longer
duration from diagnosis (>2years) comapred to those with shorter duration from
diagnosis (<1year). On the other hand, the serum activities of ALP and HSAP were
significantly higher in patients with diagnosis >2years compared to those with duration
of <1year after diagnosis (P<0.01).
Table 3: Comparison of the mean levels of the biochemical parameters in prostate
cancer subjects with respect to duration from diagnosis:
Parameter |
Duration |
<1year (n = 20) |
1-2 years (n = 14) |
>2 years (n = 13) |
PSA (ng/ml) |
12.7± 5.1a |
10.1 ± 2.8b |
7.8 ± 2.6b |
ACP (U/L) |
82.7 ± 41.7a |
51.8 ± 23.0b |
49.1 ± 19.1b |
PAP (U/L) |
78.0 ± 41.5a |
48.4 ± 19.7b |
44.2 ± 17.1b |
ALP (U/L) |
222.2 ± 61.7a |
250.8 ± 50.3a |
298.1 ± 42.5b |
HSAP (U/L) |
0.9 ± 0.6a |
1.3 ± 0.9a |
4.3 ± 2.3b |
| Values
are mean ± SD |
| Values
with different superscripts per row are statistically significant (P<0.05) |
Comparison of serum PSA and phosphatase
isoenzymes activity shows that for each age group, (Table 4) the values were significantly
higher in patients than in controls (P<0.01 and P<0.001).
| Table 4: Age-wise distribution of serum biochemical values in prostate
cancer patients and controls |
| Parameter |
Age Groups |
51-60 years |
61-70 years |
71-80 years |
81-90 years |
Patients (n=6) |
Controls (n=22) |
P value |
Patients (n=18) |
Controls (n=20) |
P value |
Patients (n=21) |
Controls (n=19) |
P value |
Patients (n=2) |
Controls (n=10) |
P value |
| PSA
(ng/ml) |
7.3 ± 2.7 |
2.5 ± 0.9 |
<0.01 |
9.3 ± 3.0 |
2.3 ± 0.5 |
<0.001 |
11.9 ± 4.0 |
1.9 ± 0.7 |
<0.001 |
18.0 ± 8.0 |
2.1 ± 0.7 |
<0.01 |
| ACP (U/L) |
61.4 ± 33.8 |
8.8 ± 4.3 |
<0.001 |
60.1 ± 26.5 |
8.4 ± 3.5 |
<0.001 |
66.8 ± 40.4 |
6.7 ± 2.2 |
<0.001 |
82.2 ± 44.1 |
7.7 ± 2.3 |
<0.001 |
| PAP (U/L
) |
57.6 ± 33.9 |
3.1 ± 2.7 |
<0.001 |
53.5 ± 24.4 |
2.9 ± 2.2 |
<0.001 |
62.9 ± 39.7 |
1.8 ± 1.9 |
<0.001 |
77.8 ± 42.4 |
2.2 ± 1.3 |
<0.001 |
| ALP (U/L) |
206.2 ± 92.9 |
153.1 ± 63.2 |
>0.05 |
249.8 ± 55.2 |
117.2 ± 51.9 |
<0.001 |
263.7 ± 54.9 |
120.6 ± 45.8 |
<0.001 |
279.9 ± 0.5 |
145.8 ± 51.7 |
<0.01 |
| HSAP
(U/L) |
0.4 ± 0.3 |
0.00 ± 0.0 |
<0.01 |
1.0 ± 0.9 |
0.0 ± 0.0 |
<0.001 |
2.6 ± 1.2 |
0.0 ± 0.0 |
<0.001 |
4.6 ± 2.1 |
0.0 ± 0.0 |
<0.001 |
| Values are mean ± SD |
Results of this study indicate significant elevations in serum PSA
concentrations as well as ACP, PAP, ALP and HSAP activities in prostate cancer patients
compared to controls. It shows that PSA remains a potent marker for diagnosis of prostate
cancer. However, ALP and HSAP, and of course ACP and PAP may be effective markers for
prostate carcinoma with reliability in the range of PSA (85.1%) > PAP (66.0%) > ACP
(57.5%) > ALP (34.0%) > HSAP (21.3%). The higher reliability shown by PSA, PAP, and
ACP may be due to the fact that they are prostate specific proteins.16,17 The
continued use of ACP and PAP assays due to the absence of PSA assay facility may account
for the reported low incidence of prostate carcinoma in Nigeria.18
Higher levels of ALP and HSAP activities in patients with longer
duration of prostatic cancer corroborates the finding that increases in serum levels of
ALP occur with concomitant advancement of prostate cancer.19 This may be due
to, not only elevation in serum HSAP, but also increase in the concentration of bone and
liver ALP isoenzymes in advanced prostate carcinoma with bone and liver metastasis
respectively.20 Increase in ALP and HSAP with advanced prostate cancer may make
ALP and HSAP as markers of relapse during treatment. Elevated levels of HSAP appear to
occur in prostate cancer patients with metastatic disease that are clinically progressive
as well as those apparently responding to chemotherapy.8,21 The lower mean
values of PSA, PAP and ACP in the prostate cancer subjects with longer duration after
diagnosis may indicate that these may be better indices of the organ’s response to
treatment of the tumour. Therefore PSA is a useful marker in the management of patients
with prostate carcinoma and it surpasses PAP in this regard.22
An age-adjusted study of the mean PSA, ACP, PAP, ALP and HSAP
values in the prostate cancer patients showed higher levels with higher age of the
subjects. The mean values of PSA, PAP and ACP showed statistically significant higher
values in the prostate cancer patients compared to control subjects in all age groups,
while the increase in ALP was not statistically significant in the youngest age group
(51-60 years). This further confirms the greater reliability of PSA, PAP and ACP in the
prostate cancer monitoring over ALP. The significant increases observed among the older
age groups may be attributed to the finding that prostrate cancer is the most common
malignant tumour in Nigerian men of average age 71 years.7
This study has confirmed that PSA measurement remains a more reliable
method compared to ACP, PAP, ALP and HSAP assays for the diagnosis of prostate cancer. It
also points to the issue that spectrophotometric measurement of PAP and ACP, and may be
ALP and HSAP could be relevant in the monitoring of patients with prostate cancer. It
calls for the inclusion of PSA measurement in the litany of tests run in most hospitals in
Nigeria for the diagnosis of prostate cancer. This will help bring into focus the exact
incidence of prostate cancer in Nigeria for adequate management and planning.
- Pienta KJ, Demers R, Holf M, Kan TY, Motie JE, Severson RK. Effects of age and race on
the survival of men with prostrate cancer in the Metropolitan Detroit tricounty area, 1973
to 1987. Urology. 1995;45:93-101.
- Ahluwalia BS, Jackson MA, Jones GW, William AO, Rao MS, Rajguru S. Blood hormone
profiles in prostate cancer patients in high-risk and low – risk population. Cancer.
1981;48:2267-2273.
- Osegbe DN. Prostate cancer in Nigerians: facts and non-facts. J Urol.
1997;157:1340-1343.
- Ogunbiyi JO., Shittu OB. Increased incidence of prostate cancer in Nigerians. J Natt
Med Assoc. 1999;91:159-164.
- Sun T, Lam KW, Narukor L. Clinical applicability of acid phosphatase isoenzyme assay. Clin
Chem. 1981;27:1742-1744.
- Morote RJ, de Torres MJA. Determination of prostatic specific antigen and prostatic acid
phosphatase as tumour markers of cancer of the prostate. Arch Esp Urol.
1989;42:124-130.
- Eke N, Sapira MK. Prostate cancer in Port Harcourt, Nigeria: features and out come. Urology.
2002;4:1-2.
- Slack NH, Chu TM, Wajsman LZ, Murphy GP. Carcinoplacental isoenzyme (Regan) in carcinoma
of the prostate. National prostate cancer project. 1981;41:146-151.
- Schmidt JD, Slack NH, Chu TM, Murphy GP. Placenta – like isoenzyme of alkaline
phosphate in prostatic cancer. J Urol 1982;127:457–459.
- Moss DW, Henderson A, Kachmar JF. Enzymes. In Tietz NW. ed. Fundamentals of Clinical
Chemistry. Philadelphia: WB Saunders Co, 1987. pp310-313, 329-332.
- Moss DW, Whitby LG. A simplified heat inactivated method for investigating alkaline
phosphatase isoenzymes in serum. Clin Chem Acta 1975;61:63–71.
- Varley H, Gowenlock AH, Bell H. Enzymes. In William H ed. Practical Clinical
Biochemistry. London: William Heinemann Med Books Ltd, 1980. p 813–818.
- Vashi AR, Wojno KJ, Henicks W, England BA, Vessella RL, Lange PH, et. al.
Determination of the "reflex range" and appropriate cut-points for percent free
prostate-specific antigen in men referred for prostatic evaluation using the AxSYM system.
Urology. 1997;49:19-27.
- Dupont A, Cusan L, Gomez JL, Thibeault MM, Tremblay M, Labrie F. Prostate specific
antigen and prostatic acid phosphatase for monitoring therapy of carcinoma of the
prostate. J Urol. 1991;146:1064-1068.
- Nduka N. Clinical Biochemistry for Students of Pathology. Longman Nigeria Plc, Nigeria.
1999; 225-228.
- Bauer HW. Acid phosphatase, alkaline phosphatase and prostate – specific antigen:
usefulness in diagnosis of metastatic disease and follow–up. Prog Clin Biol Res.
1988;269:33–42.
- Way BA, Kesseler G. Tumour marker overview. Laboratory Medicine Newsletter. 1996; 4: 9.
- Ekwere PD, Egbe SN. The changing pattern of prostate cancer in Nigerians: current status
in the southeastern states. J Natl Med Assoc. 2002;94:619-627.
- Gadre SG, Kale KU, Hedge R, Raste AS. Comparative study of alkaline phosphatase and
prostate specific antigen in prostate cancer. Indian J Med. Sci. 2000;54:136-139.
- Wajsman Z, Chu TM, Bross D, Saroff J, Murphy GP, Johnson DE, Scott WA, Gibbons RP, Prout
GR, Schmidt JD. Clinical significance of serum alkaline phosphatase isoenzymes levels in
advanced prostate carcinoma. J Urol. 1978;244-246.
- Tucci A, Saviano C, Del-Prete S. Role of alkaline phosphatase Regan isoenzyme in
prognosis of patients with osteosarcoma. Medicina (firenze). 1990;10:158-160.
- Filella X, Molina R, Jo J, Umbert B, Bedini JL, Ballesta AM. Clinical usefulness of
prostate-specific antigen and prostatic acid phosphatase in patients with prostatic
cancer. Tumour Biol. 1990;11:289-294.
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