Prostate-specific acid phosphatase

Hakalahti, L., and Vihko, P. (1989). Purification of monoclonal antibodies raised against prostate-specific acid phosphatase for use in vivo in radioimaging of prostatic cancer. ]. Immunol. Methods 117, 131-136. 

Prostatic Acid Phosphatase/Prostate-Specific Acid Phosphatase... 

Prostate-specific acid phosphatase (PSAP) is one of the earlier prostate lineage markers that was exploited for immunolabeling of PCa before the discovery of PSA. Currently, its use as a marker of prostatic differentiation has declined given its relative lack of specificity compared with PSA and the more variable staining of PSAP in higher-grade PCa. > ... 

Vernon SE, Williams WD. Pre-treatment and post-treatment evaluation of prostatic adenocarcinoma for prostatic specific acid phosphatase and prostatic specific antigen by immunohis-tochemistry. J Urol. 1983 130 95. 

Svanholm H. Evaluation of commercial immtmoperoxidase kits for prostatic specific antigen and prostatic specific acid phosphatase. Acta Pathol Microbiol Immunol Scand [A]. 1986 94 7. 

Epstein JI, Kuhajda FP, Lieberman PH. Prostate-specific acid phosphatase immunoreactivity in adenocarcinomas of the urinary bladder. Hum Pathol. 1986 17 939. 

Hammond ME, Sause WT, Martz KL, et al. Correlation of prostate-specific acid phosphatase and prostate-specific antigen immunocytochemistry with strrvival in prostate carcinoma. Cancer. 1989 63 461. 

Prostate carcinoma Acid phosphatase (ACP) Prostate specific antigen (PSA)... 

Red blood cells also contain sufficient acid phenylphospha-tase for mild hemolysis to cause false elevations. Therefore, inhibitors such as ethanol, formaldehyde, copper sulfate> and 1-tartrate have been used to inhibit selectively the enzyme of one or more tissues and enhance the specificity of the test (101). Ethanol is unsuitable because it inhibits the enzyme from erythrocytes and prostate simultaneously, and because it yields serum activities which correlate poorly with prostatic disease. Formaldehyde inhibits the erythrocytic enzyme and has been said to yield clinically satisfactory results. The copoper resistant acid phosphatase of serum is elevated by metastatic carcinoma of the breast, as well as by other metastatic cancers, and is also elevated by a wide variety of non-cancerous diseases. 

Babson proposed a-naphthyl phosphate as an essentially specific substrate for the activity of prostatic acid phosphatase in serum (104). However Marshall, Price, and Amador found that this substrate is not specific for the prostatic enzyme because urine of human females contain 50 times more acid a-naphthyl phosphatase than male serum and 50% as much activity as male urine. Platelets have significant activity and the serum activity can increase to abnormal values following clotting. These workers also observed elevated activities in females with skeletal metastases of the breast. In 50 hospitalized male patients who had no evidence of prostatic cancer and 25 hospitalized female patients, the incidence of false positive results was 12%, a magnitude sufficient to preclude meaningful clinical interpretation (105). 

Roy, A. V. Brown, M. E. and Hayden, J. E. Sodium thymolphthalein monophosphate, a new acid phosphatase substrate with greater specificity for the prostatic enzyme in serum. Clin. Chem. (1971), IJ, 1093-1102. 

Note PCa, prostate cancer WM, white male DES, diethylstilbestrol AR, androgen receptor PSA, prostate specific antigen and PAP, prostatic acid phosphatase. 

Acid phosphatase (acid phosphomonoesterase, EC 3.1.3.2) also catalyzes the hydrolysis of phosphoric acid monoesters but with an acidic pH optimum. It has broad specificity and catalyzes transphosphorylations. Acid phosphatases are a quite heterogeneous group with monomeric, dimeric, larger glycoprotein, and membrane-bound forms. Acid phosphatase activity is present in the heart, liver, bone, prostate, and seminal fluid. Prostate carcinomas produce large quantities of acid phosphatase, and the enzyme is, therefore, used as a biomarker [141]. 

Provenge is a cancer vaccine using cell therapy technique. Dendritic cells are removed from patients. These cells are treated with the prostate-specific antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cases. The activated dendritic cells are returned to the patients and they stimulate the T cells to destroy cancer cells expressing the PAP, thus treating the tumor. 

Acid phosphatase retains its activity for a long period and hence is useful in forensic science to detect semen but has now been superseded by DNA fingerprinting. The activity in blood was used in the diagnosis of prostatic cancer but was superseded by PSA (prostate specific antigen). 

Prostate-specific anfigen, acid phosphatase, alk phosphatase... 

Acid phosphatases are produced by erythrocytes, the liver, kidney, spleen, and prostate gland. The enzyme of the prostate gland is clinically important, because its increased activity in the blood can be an indication of prostate cancer. The phosphatase from the prostate gland is strongly inhibited by tartrate ion, but acid phosphatases from other tissues are not. How can this information be used to develop a specific procedure for measuring the activity of the acid phosphatase of the prostate gland in human blood serum ... 

Group Substrate Normal range (units/100 ml) Serum plus prostatic acid phosphatase Serum plus erythrocytic acid phosphatase Heated serum Relative specificity for prostatic acid phosphatase... 

A spectrofluorometric method for the estimation of acid phosphatase has been devised. It uses a-naphthyl phosphate as substrate thus, it is somewhat more specific for prostatic acid phosphatase than most (37). 

Takayama TK, McMullen BA, Nelson PS, Matsumura M, Fujikawa K. Characterization of hK4 (Prostase), a prostate-specific serine protease Activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. Biochemistry 2001 40 15341-15348. 

Forensic biochemists perform blood typing and enzyme tests on body fluids in cases involving assault, and also in paternity cases. Even tiny samples of blood, saliva, or semen may be separated by electrophoresis and subjected to enzymatic analysis. In the case of rape, traces of semen found on clothing or on the person become important evidence the composition of semen varies from person to person. Some individuals excrete enzymes such as acid phosphatase and other proteins that are seldom found outside seminal fluid, and these chemical substances are characteristic of their semen samples. The presence of semen may be shown by the microscopic analysis for the presence of spermatozoa or by a positive test for prostate specific antigen. 

Because the intermediary metabolism of various organs is virtually the same, organ-specific enzymes are very rare. One example usually cited is the acid phosphatase of the prostate. However, the enzyme complement of the various organs may differ with respect to relative activities of the enzymes, the time dependence of their appearance in plasma, and the pattern of their isoenzymes (see below). Table 5.2 presents a list of enzymes commonly used for organ- and disease-specific diagnoses. 

Other enzymes are also useful indices of liver pathology. Serum alkaline phosphatase is often a useful indicator of liver and bone disease. The alkaline phosphatases are a diverse group of enzymes that catalyze reactions in which a phosphate is removed from a phosphate ester, especially at an alkaline pH. Physicians don t care about this. They do care that serum alkaline phosphatase levels often rise with bone breakdown (as in tumor infiltration) and in liver disease, especially where tliere is obstruction of the bile duct. Acid phosphatase is particularly rich in the prostate. A rise in its serum levels provides a test as to the presence of prostate carcinoma. This test has largely been replaced by assay for Prostate Specific Antigen (PSA), a serine protease that is elevated in prostatic carcinoma. 

Prostate Adenocarcinomas Prostate-Specific Antigen (PSA) (25) Prostatic acid phosphatase (PAP)... 

The question may arise as to which is the preferred method. In the author s experience, and this will be documented more completely later, the use of the substrate, sodium (S-glycerophosphate, as in the Bodansky procedure (B18, 32), is more specific for elevations of serum acid phosphatase activity due to prostatic carcinoma. However, the use of other substrates, such as sodium phenyl phosphate in the Gutman method (GIO, G14), may elicit alterations of activity in the serum that reflect diseases in other tissues. 

Specificity of Serum Acid Phosphatase Determination fob Carcinoma of the Prostate... 

In addition to the studies cited above, there are several others showing that phenyl phosphate is much more readily hydrolyzed than j3-glycerophosphate by acid phosphatase from human erythrocytes, whereas no such marked difference exists with respect to human prostatic phosphatase (B2, Tl, T3). Unfortunately, there do not appear to be any systematic investigations of the substrate-velocity relationship for the acid phosphatases of other human tissues. In general, the available data would indicate that /3-glycerophosphate is a more specific substrate than phenyl phosphate for the detection and assay of acid phosphatase coming from the prostate. 

Another procedure to increase the specificity of acid phosphatase determinations for prostatic disease has involved the use of n- (-I-) -tartrate to distinguish between the enzyme from the prostate and other tissues. In a series of papers from 1947 to 1949, Abul-Fadl and King (Al, A2, A3, A4) studied the properties of various acid phosphatases and reported that 0.01 Af L- (4-) -tartrate inhibited the hydrolysis of phenyl phosphate by human prostatic acid phosphatase dissolved in normal saline or in plasma to the extent of 95%, but had no effect on the hydrolysis by acid phosphatase from erythrocytes. The inhibitions of acid phosphatases from other human tissues were as follows liver, 70% kidney, 80% spleen, 70%. 

T3. Tsuboi, K. K., and Hudson, P. B., Acid phosphatase. III. Specific kinetic properties of highly purihed human prostatic phosphomonoesterase. Arch. Biochem. Biophys. 55, 191-205 (1955). 

Alkaline phosphatase is one of the most suitable enzymes for electrochemical immunoassays owing to its high turnover number and broad substrate specificity. Different substrates have been used, but 4-aminophenyl phosphate is most suitable, since the reaction product, 4-aminophenol is easily oxidized without fouling of the electrode surface. Thyroxine-binding globulin, cortisol, and prostatic acid phosphatase have been detected by using alkaline phosphatase. 

Efforts to obtain tumor-selective cytostatic agents, based on a selective bioactivation in the malignant tissues, have not been very successful up to now. This is mainly due to a lack of enzyme specificity in malignant tissues as compared to healthy vital tissues. Diethylstilbestrol, an estrogen, is active against tumors of the prostate. The phosphate ester of diethylstilbestrol, Honvan, is inactive but is converted to the active product by the acidic phosphatase that is abundant in the prostate tissue. The enzyme concerned, however, is not restricted to the prostate kidney and bone tissues are also rich in acidic phosphatase, so that the bioactivation is not restricted to the target tissue. 

Wlien comparing two procedures, confusion is avoided by using the ROC curves instead of accepting statements such as Test A is more sensitive, but Test B is more specific. For example, the usefulness of the prostatic acid phosphatase assay has been compared for years with that of the PSA assay for diagnostic and foUow-up purposes. Various claims have been made regarding the relative sensitivity and specificity of the two assays. 

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