Disease, acid phosphatase activity

G8. Goldfischer, S., Liver celi lysosomes in Wilson s disease acid phosphatase activity by light and electron microscopy. Am. J. Pathol. 43, 511-518 (1963). 

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. 

The slight but definite elevations of serum acid phosphatase activity in conditions such as thrombocytopenia (02, Zl), Gaucher s disease (T6, T8), or various myeloproliferative diseases (B6) indicate the possibility that platelets, the marrow, and the reticuloendothelial system may also be sources of acid phosphatase. These aspects will be discussed more fully later in the review. 

Carcinoma of the prostate is today one of the three most frequent causes of death from neoplastic disease in men in the United States (G4). The early studies of Gutman and his associates (Gil, G12, R6, S30) established that serum acid phosphatase activity was elevated very frequently in patients with metastatic carcinoma of the prostate. It is of interest to consider briefly the uncertainties inherent in the development of this relationship. Skeletal metastases, if sufficiently large, are of course detectable by roentgenographic examination, but smaller ones may not be, and metastases to soft tissues may likewise be undetectable. For example, in 15 cases of metastazing carcinoma reported by Gutman... 

Elevations op Serum Acid Phosphatase Activity in Diseases OP THE Prostate... 

In 1956, Fishman et al. (F2) summed up their experience with a series of 91 cases of proven cancer of the prostate and a total of 1198 patients with other diseases. Of these 91 cases, 32, or 35%, had elevated total serum acid phosphatase activities. This incidence was much lower than that, 85%, reported by Sullivan et al. (S30) in 1942 or the value of 89% reported by Herbert (H5) in 1946 for patients with carcinoma of the prostate and skeletal metastases. These investigators had used the method of Gutman and Gutman (GIO, G14), which was essentially the same method as that employed by Fishman and Lerner (FI) and gave the same ranges of normal values (Table 6). The possibility existed that treated cases had normal total serum phosphatase activities and thus weighted the overall incidence toward a low value. However, the data of Fishman et al. (F2) show that the incidence of total serum acid phosphatase activities in treated cases was 20/52, or 38%, even higher than the incidence 12/39, or 31%, in the untreated cases. 

Whatever may be the reason for the low incidence of elevations of total serum acid phosphatase activity in Fishman and his associates (F2) series of proven cases of carcinoma, the higher incidence of elevations of prostatic acid phosphatase activity indicates that in the patients of this series the determination of the latter was a more sensitive indicator of the presence of prostatic carcinoma. Moreover, when serum prostatic acid phosphatase activities were determined during the course of a patient s illness, they paralleled the exacerbation or remission of the disease. Whitmore et al. (W4) have considered the relationship of clinical status to the total and prostatic acid phosphatase activities in 20 patients with proven carcinoma of the prostate. 

Acid Phosphatase Activity in Nonphostatic Disease 6.6.1. Introduction... 

The term serum has been omitted designedly from the title of this section, for we shall be discussing not only alterations of acid phosphatase activity in the serum of patients with nonprostatic disease, but also in the leukocytes of patients with hematologic and hematopoietic disorders and, in some conditions, in certain specialized tissues. 

The possibilities that cryptic prostatic carcinoma may coexist with other diseases or that a high serum alkaline phosphatase activity possesses some residual activity at pH 5.0 tend to be negated by an analysis of these five patients. One female with carcinoma of the breast and osteolytic metastases of the femur, pelvis, and spine had an elevated serum acid phosphatase activity of 4.2 K.A. units, and a second female with an unknown primary but with osteolytic lesions of the ribs and scapula had an activity of 4.1 K.A. units. The serum alkaline phosphatase activities were 17.8 Bodansky units in the first case and 5.2 Bodansky units in the second case, both above 4.2 Bodansky units, the upper limit of normal values by this method. 

One female and one male patient had hyperparathyroidism with elevated serum alkaline phosphatase activities and extensive bone changes characteristic of generalized osteitis fibrosa cystica. In both instances, the serum acid phosphatase activity of the serum fell to normal values after removal of the parathyroid adenoma despite transitorily increased serum alkaline phosphatase activity. The fifth patient was a female with osteopetrosis involving the major part of the skeleton. The serum acid phosphatase was 8.7 K.A. units, the highest in the control series— yet the serum alkaline phosphatase was within normal limits. It would appear, therefore, that some patients with skeletal disease may have a slight but definitely elevated serum acid phosphatase activity, at least as determined by the Gutman method (GIO, G14), which cannot be explained by concurrent prostatic carcinoma or by a spillover of alkaline phosphatase activity to a pH of 5.0. 

Table 10 shows the distribution of serum acid phosphatase activities in neoplastic disease other than prostatic cancer. The incidences of elevations were 19% in patients with skeletal metastases 2% in pa-... 

Using the Bodansky (B18, 52) procedure with 8-glycerophosphate as substrate, Woodard (W8) was unable to obtain such elevations. She determined the serum acid phosphatase activities in 83 females and 342 males, or a total of 425 patients with miscellaneous diseases. Of these, 61 had various types of infectious or metabolic disorders, including 11 cases of inflammatory disease of bone and 12 cases of hepatic cirrhosis. The remainder had some type of neoplastic disease and about one-third had metastases to bone from cancer of various primary sites. There were 15 cases of osteogenic sarcoma and 32 cases of osteitis deformans. All these cases, whether their serum alkaline phosphatase activities were elevated or not, had serum acid phosphatase values that were essentially within the normal range, 0.06-0.89 Bodansky unit for females and 0.11-0.88 unit for males. In contrast to the Gutman method (GIO, G14), there-... 

Of considerable interest were the much higher incidences of elevated acid phosphatase activities in patients with nonprostatic, metastatic neoplastic disease. For example, in 70 female patients with metastatic carcinoma of the breast, the range of activities was 7.3 to 101 units, with 74% of the patients showing elevated activities. In 48 males with nonprostatic metastatic carcinoma and in 42 females with nonmammary metastatic carcinoma, the incidence of elevated acid phosphatase activities were 46% and 31%, respectively. 

The report of these high incidences of elevations of acid phosphatase activity in miscellaneous disease and in nonprostatic neoplastic disease, determined by a method presumably more specific than the usual Gutman method (GIO, G14), is not in accord with earlier studies, such as those of Sullivan et al. (S30) shown in Table 10. The incidences of elevations were considerably lower than those reported by Reynolds et al. 

Sebum and Plasma Acid Phosphatase Activity in Hematologic and Hematopoietic Disease... 

In 1957, Tuchman and Swick (T6) reported the finding of elevated serum acid phosphatase activities, ranging from 7.0 to 10.3 K.A. units in a 68-year-old man, who was first suspected of having carcinoma of the prostate. The diagnosis of Gaucher s disease was then considered and confirmed by a sternal marrow aspiration. By 1959, Tuchman et al. (T7)... 

Leukocyte Acid Phosphatase Activity in Various Hematologic Diseases ... 

Although serum acid phosphatase activity has already been considered in certain diseases of childhood, such as leukemia or Gaucher s disease, it may be of value to make several general comments in this area. Laron and Kowadlo (L4) found that the mean normal values for total serum acid phosphatase were 5.23 1.26 K.A. units for children 1 year of age and 4.63 0.93 K.A. units for children 2-8 years of age. These are higher than the values for adults. The mean value for l- (-I-) -tartrate-inhibited acid phosphatase activity was 0.21 0.28 K.A. units for all age groups. 

G12. Gutman, A. B., Gutman, E. B., and Robinson, J. N., Determination of serum acid phosphatase activity in differentiating skeletal metastases secondary to prostatic carcinoma from Paget s disease of bone. Amer. J. Cancer 38, 103-108 (1940). 

L4. Laron, Z., and Kowadlo, A., Serum total and i.(-l-)-tartaric-acid-inhibited acid-phosphatase activity in various diseases of childhood. Acta Paediat. (Stockholm) 50, 371-376 (1961). 

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