Cancer prostatic acid phosphatase

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). 

Ying, S. H. and Day, E. Serim prostatic acid phosphatase levels in proved cases of carcinoma or benign hypertrophy of the prostate. Cancer (1956), , 228-233. 

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

Lin M-F, Meng T-C, Rao PS, et al. Expression of human prostatic acid phosphatase correlates with androgen-stimulated cell proliferation in prostate cancer cell lines. J. Biol. Chem. 1998 273 5939-5947. 

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. 

Table 9 shows the number of abnormal total and prostatic acid phosphatase values in male individuals who had presented themselves at a cancer clinic and who on examination showed no benign prostatic hypertrophy (D6). Because of the possibility that, in accordance with Fishman and his associates concept (F3), these abnormal values for the prostatic portion might be a forerunner of advancing disease, determinations were repeated after various intervals. The individual with an initial prostatic acid phosphatase value of 1.14 units showed a value of 0.36 units 5 weeks later and a value of 0.30 units 6 weeks after his first visit. 

D6. Day, E., Ying, S. H., Schwartz, M. K., Whitmore, W. F., Jr., and Bodansky, O., Serum prostatic acid-phosphatase levels in the male patients of a cancer-proven-tion clinic. Cancer 9, 222-227 (1956). 

Seamonds B, Yang N, Anderson K, Whitaker B, Shaw LM> Bollinger JR. Evaluation of prostate-specific antigen and prostatic acid phosphatase as prostate cancer markers. Urology 1986 28 472-9. 

The ProstAsure index, developed by Zhang, Stamey, and Chan, was designed to increase the sensitivity and specificity of cancer detection, while maintaining a reasonable false positive detection rate. The index is derived firom several values, including age, total PSA, creatine kinase isoenzymes, and prostatic acid phosphatase, which are input... 

Machlenkin, A. Paz, A. Bar Haim, E. Goldberger, O. Finkel, E. Urosh, B. Volovitz, I. Vadai, E. Lugassy, G. Cytron, S. Lemonnier, F. Tzehoval, E. Eisenbach, L., Human ctl epitopes prostatic acid phosphatase-3 and six-transmembrane epithelial antigen of prostate-3 as candidates for prostate cancer immunotherapy, Cancer Res. 2005, 65, 6435-6442... 

Acid phosphatases are enzymes that have been studied extensively due to the fact that their dysregulation is associated with pathophysiological conditions. This characteristic has been exploited for the development of diagnostic and therapeutic methods. As an example, prostatic acid phosphatase was the first marker for metastatic prostate cancer diagnosis and the dysregulation of tartrate resistant acid phosphatase is associated with abnormal bone resorption linked to osteoporosis. 

Quintero IB, Araujo CL, Pulkka AE et al (2007) Prostatic acid phosphatase is not a prostate specific target. Cancer Res 67 6549-6554... 

Lin ME, DaVolio J, Garcia-Arenas R (1992) Expression of human prostatic acid phosphatase activity and the growth of prostate carcinoma cells. Cancer Res 52 4600-4607... 

Sobin LH, Hjermstad BM, Sesterhenn lA, Helwig EB. Prostatic acid phosphatase activity in carcinoid tumors. Cancer. 1986 58 136. 

Heyderman E, Brown BM, Richardson TC. Epithelial markers in prostatic, bladder, and colorectal cancer an immunoper-oxidase study of epithelial membrane antigen, carcinoembry-onic antigen, and prostatic acid phosphatase. J Clin Pathol. 1984 37 1363. 

Sidhu J, Sanchez RE. Prostatic acid phosphatase in strumal carcinoids of the ovary An immunohistochemical study. Cancer. 1993 72 1673-1678. 

Burch PA et al. Immunotherapy (APC8015, Provenge) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer a Phase 2 trial. Prostate 2004 60 197-204. 

Acid- and alkaline phosphatases act on a variety of mono- and multiple phosphate carrying low molecular mass molecules. In addition, they hydrolyze many, but not all, phosphoproteins. They are in use for decades to easily screen for diseases, however, somewhat unspe-cifially. For instance, acid phosphatase is used as biomarker for prostate cancer, and alkaline phosphatase to monitor bone (de-) mineralization and liver tumors. 

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. 

Hill, J. H. Prostatic serum acid phosphatase in patients with localized prostatic cancer. Am. J. Clin. Path. (1956), 26, 120-130. 

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). 

E. Therapeutic response In prostate cancer, a complete response is considered to be disappearance of tumor masses, normalization of elevated acid phosphatase, disappearance of osteoblastic lesions, recal-cihcation of osteolytic lesions, and normalization of hepatomegaly and abnormal... 

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 ... 

Isozymes are enzymes from different organs of the organism that perform the same function. They may have different Km s for the substrate they use. Prostatic cancer is diagnosed by acid phosphatase measurements (see Table 5.2). 

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. 

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