Prostatic acid phosphatase (PAP)

Characteristics

Human prostatic acid phosphatase (PAP) is a glycoprotein synthesized in the glandular epithelial cells of the prostate. The gene encoding PAP is located at chromosome 3q21 ® qter. Native PAP exists as a dimer of two catalytically inactive subunits which are non-covalently bound together to form an active enzyme.
PAP exists in two forms, intracellular and secreted. PAP is secreted in large amounts into seminal fluid, and the serum activity of the enzyme is frequently elevated in patients with prostate adenocarcinoma. Since PAP is present in large quantities in spermatic fluid, it has been attributed a physiological role in fertility and it may affect the mobility of sperm. Cellular PAP has been implicated to be involved in the growth regulation of prostate cells.
PAP immunoreactivity in the normal prostate has been located to lysozymes in the apical area of the columnar, secretory cells of the prostatic acini and ducts. Immunoreactivity is more intense and homogenous in benign prostate than in cancer. No PAP can be demonstrated in transitional, stromal or basal cells. Metaplastic squamous epithelial cells are usually negative for PAP, in rare cases faintly positive.
PAP is characterized by a high organ specificity, but not as high as prostate specific antigen. Most extraprostatic tissues displaying PAP immunoreactivity are derived form cloaca: periurethral and anal glands and the urachus. Furthermore, PAP has been demonstrated in scattered neuroendocrine cells of the colon-rectum, renal tubular cells, pancreatic islet cells, hepatocytes, gastric parietal cells, duct epithelium of the breast and in cystitis cystica and cystitis glandularis as well as in some leukocytes, particularly neutrophils.

Neoplasms

PAP can be readily demonstrated in the epithelial cells of prostatic adenocarcinoma, usually homogenously and with strong staining intensity. Well differentiated carcinomas express more PAP antigens than poorly differentiated tumours. Less than 2% of poorly differentiated carcinomas are negative for PAP immunoreactivity. PAP reactivity in bone metastasis has been poorer after decalcification than PSA staining under the same conditions.
Adenocarcinoma and mixed urothelial/adenocarcinoma of the urinary bladder may react with antibodies to PAP. Known extraprostatic tumours reported reacting with PAP antibodies include islet cell tumours of the pancreas and rectal carcinoid tumours.

Application

PAP antibodies are useful in identifying and localizing prostatic adenocarcinoma in the prostate, urinary bladder and rectum, and at metastatic sites in cases of unknown primary tumour. Its utility is somewhat decreased by reactivity with non-prostatic neoplasms described above and it has been replaced in many laboratories by PSA.

Visualization

mAb PASE/4LJ and pAb A0627 (DakoCytomation) has shown to give optimal results in Run 12.

Other mAbs are P-29, SB19, 501, 503, 504, 045, PAP29, PAY376, 8, PAP12, PAP29 and ZMPAP4.

Abs raised against seminal fluid show weak reactivity with seminal vesicles; this is not seen with antibodies to epitopes in prostatic epithelium.
Recommended control tissue: normal prostate supplemented with a prostate adenocarcinoma known to express a low level of PAP (typically a high grade tumour). It is also advisable to include kidney to verify the specificity of the protocol (particularly if using a biotin based detection system) and the sensitivity, as distal tubules only weakly express PAP.

Assessments

Run 12 2004

Selected references

Epstein JI. PSA and PAP as immunohistochemical markers in prostate cancer. Urol Clin North Amer 1993;20:757-770.
Kidwai N, et al. Expression of androgen receptor and prostate-specific antigen in male breast carcinoma. Breast Cancer Res 2004;6:R18-R23.
Parwani AV, et al. Prostate carcinoma with squamous differentiation: an analysis of 33 cases. Am J Surg Pathol 2004;28:651-657.