Serum concentrations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) were measured in 51 liver cirrhosis, 37 chronic active hepatitis.
Intemational Urology and Nephrology 28 (1), pp. 67-71 (1996)
Prostatic Acid Phosphatase and Prostate Specific Antigen in Liver Disease A. KADAYIFCI, M. BENEKLI, H.
SIM~EK,
O. SENCAN
Department ofIntemal Medicine, Hacettepe University Medical School, Ankara, Turkey (Accepted September 16, 1995)
Serum concentrations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) were measured in 51 liver cirrhosis, 37 chronic active hepatitis (CAH) patients and 26 healthy individuals. Elevated PSA levels have been found in 2 of cirrhotic patients while no increase has been detected in CAH and controls. Serum PAP levels have been observed slightly increased in 2 patients with cirrhosis, 2 patients with CAH and 1 control case. Mean PSA and mean PAP values showed no significant difference between groups (p>O.05). Serum PSA and PAP levels are reliable in diagnosing and monitoring prostate cancer in chronic liver patients and maintain their specificity in this situation.
Introduction
\.
Prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) are tumour markers used as an adjunct in the clinical diagnosis of prostatic carcinoma, as a prognostic tool, and in the long-term monitoring of patients after therapy [1]. PAP is a glycoprotein, normally secreted from the prostate gland. PSA is a glycoprotein serine protease and has been shown to improve greatly the detection of prostate cancer when combined with PAP [2]. Serum levels of PAP and PSA are transiently elevated in urinary retention, following prostatic surgery, digital rectal examination and urethral catheterization. False-positive PAP and PSA elevation may be found in patients with benign prostatic hypertrophy (BPR) [3]. It is known that serum concentrations of some tumour markers glycoprotein in structure may increase in chronic liver disease due to a defect of metabolization or elimination of these molecules [4, 5]. Although PAP elevations have been noted in hepatobiliary and reticuloendothelial system disorders in a few reports [6, 7], the studies concerning PAP and PSA concentrations in liver disease are insufficient. The current investigation evaluates the sensitivity and reliability of these markers in patients with chronic liver disease, without clinical suspicion of prostate cancer.
VSP, Utrecht Akademiai Kiado, Budapest
Kadayifci et af.: PAP and PSA in liver disease
68
Patients and methods Serum samples were obtained from 88 male patients; 37 with histologically proven chronic active hepatitis (CAH) and 51 with histologically confirmed liver cirrhosis (LC). The ages ranged between 17 and 70 years (mean, 41.8±12.7) in the CAH group and 19-78 years in the LC group (mean, 49.2±16.7). Sera collected from 26 healthy men aged 18 to 61 years (mean, 43.1±15.2) were included as a control group. None of the patients and healthy subjects in the control group had clinical evidence of prostatic disease. Serum PAP and PSA were measured with commercially available ELISA kits (Enzyline diagnostic kits, Biomerieux). The selected cut-off limits were 3.5 ng/ml for PAP and 4 ng/ml PSA. All samples were stored at -20°C until assayed. The mean ± SEM of the serum PAP and PSA concentrations were compared among the CAH, LC and control groups. Student's t-test was used and p values >0.05 were not considered significant, Results The PSA serum levels were within normal limits in all of the controls and CAH patients. However, only two of 5 I patients with LC showed slightly elevated serum PSA levels (Fig. I). Mean PSA values were 0.89±0.15 ng/ml in the CAH group, 1.29±0.53 ng/ml in the LC group and 0.93±0.38 ng/ml in the control group (Table I). There was no statistically significant difference among these groups (p>0.05). Slightly elevated PAP levels were detected in
7 6
5
E c, 4
.s c:3
o,
0
3 00
2
08 88 080 000
0 08
....s.s.....-
~ 0000
00000 00000000 000000 000000 0000000 0000000
CAH
Cirrhosis
0000 00000
.... 08 8
0000 000 00000
Control
Fig. 1. Serum PSA levels in chronic active hepatitis, liver cirrhosis and control groups international Urology and Nephrology 28, 1996
69
Kadayifci et al.: PAP and PSA in liver disease Table 1 Mean values and percent increase ofPSA and PAP in CAR, cirrhosis and control groups PSA (ng/rnl)
PAP (ng/ml)
Groups
CAR Cirrhosis Control
mean±SEM
% increase
mean±SEM
% increase
O.89±O.15 l.29±O.53 O.93±0.38
0 (0/37) 4 (2/51 ) 0 (0/26)
2.34±0.41 3.35± 1.86 2.18±0.25
5 (2/37) 4 (2/51 ) 4 (l/26)
a
8
:€
6
0>
.Sa. 4 O.05). Discussion Tumour products in the clinical management of cancer were originally studied in an attempt to develop a screening test for the early detection of cancer. Modest elevation of tumour markers may be found in various non-cancerous conditions. Hepatic metastasis and hepatic dysfunction are associated with a higher proportion of abnormal levels, possibly related to a defect of metabolization or elimination of the tumour antigens. International Urology and Nephrology 28. 1996
70
Kadayifci et al.: PAP and PSA in liver disease
PAP is one of the first tumour markers employed in clinical practice for the detection of prostate cancer. However, its use has been hampered by poor sensitivity and specificity which limit the use of this marker in early stage cancer [8]. PAP may also be elevated in other neoplastic conditions such as osteogenic sarcoma, multiple myeloma and bony metastases of cancer other than prostatic [9] and non-malignant disorders such as hyperparathyroidism, osteoporosis and BPH [10]. PSA is specific for prostatic tissue but not for prostate cancer and is elevated also in BPH, precluding its sole use as a screening tool [11]. Therefore, PAP and PSA are most useful in monitoring disease and detection of metastases rather than screening. Use of both PAP and PSA greatly improves the diagnostic yield of either one used separately [2]. It is well known that compounds glycoprotein in structure are metabolized and eliminated from the liver [12]. False positive elevations of PAP and PSA concentrations can be expected in sera of patients with chronic liver disease like other glycoprotein tumour markers. In the literature there have been many reports, including ours, of false positive significant elevations of glycoprotein tumour markers such as CA 19-9 and CA 125 in liver disease, possibly due to the impaired hepatic metabolism [5, 13, 14]. However, our results with PAP and PSA in patients with CAH and LC show that these markers appear to maintain their specificity in chronic liver disease. In conclusion, in the presence of liver disease, despite the limited liver reserve, PAP and PSA are specific and reliable tumour markers which may be useful in the clinical management of prostatic carcinoma in this population. These results should be taken into account when serum concentrations ofthese markers are evaluated in liver diseases. References 1. Schwartz, M. K.: Cancer markers. In: Cancer, Principles and Practice of Oncology.
J. B. Lippincott, Philadelphia 1993. 2. Akdas, A., Simsek, F., Ilker, Y., Turkeri, L., Ercan, H.: The value of prostatic acid phosphatase and prostate specific antigen as serum markers in carcinoma of the prostate. Int. Urol. Nephrol., 25, 271 (1993). 3. Minton, J. P., Chewinsky, A.: Present status of serum markers. Sem. Surg. Oncol., 5, 426 (1989). 4. Jacops, E. L., Haskell, C. M.: Clinical use of tumor markers in oncology. Curro Prob. Cancer, 6, 301 (1991). 5. Kadayifci, A., Ozyilkan, E., Simsek, H., Sivri, B., Kayhan, 8., Ozkuyumcu, C., Telatar, H.: The elevation of serum tumor markers CA 19-9 and CA 125 in chronic liver disease type Band C. Eur. 1. Cancer, 29A (Suppl. 6),245 (1993). 6. Henneberry, M. D., Engel, G., Grayhack, J. T.: Acid phosphatase. Urol. Clin. North Am., 6, 629 (1979). 7. DiPaolo, C. J., Rival, J.: Acid phosphatase: Clinical utility of the first tumor marker. Henry Ford Hosp. Med. J., 30, 70 (1982). 8. Heller, J. E.: Prostatic acid phosphatase: Its current clinical status. J. Urol., 137, 1091 (1987). 9. Tavassoli, M., Rizo, M., Yam, L. T.: Elevation of serum acid phosphatase in cancers with bone metastasis. Cancer, 45, 2400 (1980). lntemational Urology and Nephrology 28, 1996
I.,
Kadayifci et al.: PAP and PSA in liver disease
71
acid phosphatase: 10. Cooper, J. F.: The radioimmunochemical measurement of prostatic Current state of the art. Urol. Clin. North. Am., 7, 653 (1980). antigen: Critical issues 11. Ruckle, H. C., Klee, G. G., Oesterling, J. E.: Prostate specific (1994). 59 69, Proc., Clin. for practising physicians. Mayo hepatic recognition 12. Ashwell, G., Morell, A. G.: The role of surface carbohydrates in the Mol. BioI., 41, 99 Areas Relat. Enz. Adv. teins. glicopro ng and transport of circulati (1974). in liver diseases. 13. Putzki, H., Ledwoch, J.: Tumor markers CEA, TPA, and CA 19-9 J. Surg. Oneol., 37, 133 (1987). for monitoring 14. Virji, M. A., Mercer, D. W., Herberman, R.: New immunologic markers (1989). 13 78, l., Gynaeco Chir. of cancer. Ann.
International Urology and Nephrology 28, 1996
