Prostate-Specific Antigen (PSA)

Sources/Clones
Accurate (ER-PR8), Biodesign (8), Biogenesis (PSA-001, 07), Biogenex (8), Dako (ER-PR8, polyclonal), Enzo, Hybritech, Immunotech, Oncogene (OS94.3), Oxoid (PSB535), Sanbio (8), Serotec (SC.5) and Zymed (2009).

Fixation/Preparation
The antigen is resistant to formalin fixation and immunostaining is enhanced by heat-induced epitope retrieval.

Background
Prostate-specific antigen (PSA) is a chymotrypsin-like, 33 kD singlechain glycoprotein with selective serine protease activity for cleaving specific peptides. The PSA gene is a member of the human kallikrein gene family and is located on the 13q region of chromosome 19. PSA is selectively produced by the epithelial cells of the acini and ducts of the prostatic gland and is secreted into the semen where it is directly involved in the liquefaction of the seminal coagulum that is formed at ejaculation. The sequence of PSA shows extensive homology withg-nerve growth factor (56%), epidermal growth factor-binding protein (53%) anda-nerve growth factor (51%). This feature, together with its ability to digest insulin growth factor-binding protein-III (IGFBP-3) to release biologically active IGF-I, makes PSA a candidate growth factor or a cytokine or modulator of cell growth. PSA has also recently been suggested to be capable of being produced by cells bearing steroid hormone receptors under conditions of steroid hormone stimulation (Diamandis & Yu, 1995).

Applications
PSA is a useful biochemical marker as any disruption of the normal architecture of the prostate allows diffusion of PSA into the stroma where it gains access to the peripheral blood through the microvasculature. Elevated serum PSA levels are thus seen with prostatitis, infarcts, benign hyperplasia and transiently after manipulation and biopsy. Most importantly, significant elevations are seen with prostatic adenocarcinoma, making it an important tool for diagnosis as well as monitoring response to treatment. Although cancers produce less PSA per cell than normal prostatic epithelium, the greater number of malignant cells and the disruption of stroma in the malignant gland accounts for the elevated serum PSA levels. Immunostaining for PSA has proven to be an effective method of identifying cells of prostatic origin, but the presence of PSA cannot be used to differentiate between benign and malignant. Antibodies to PSA show high sensitivity although very occasionally carcinomas have been reported to be negative for PSA. Correlations of PSA tissue reactivity with Gleason's grade of prostatic cancer have shown that high-grade tumors may be entirely negative by immunolabeling. There was an initial suggestion that the presence of PSA-negative cells in a prostatic carcinoma correlates with a more aggressive clinical course but this has not been confirmed and most tumors display very heterogeneous staining (Bostwick, 1994).

Comments
As the occasional case of prostatic carcinoma and metastatic deposit may show only weak or no staining for PSA, it is best to use this marker in conjunction with other markers of prostatic tissue such as prostatic acid phosphatase and CD 57 (Leu7). A combination of these three markers gives the highest diagnostic yield (Appendix 1.14). Furthermore, immunoreactivity to PSA has been shown in a variety of extraprostatic tissues including the epithelium of the urethra, periurethral glands of both males and females, urachal remnants, endometrium (Clements & Mukhtar, 1994), transitional epithelium of the bladder and in cystitis cystica and glandularis, anal mucosa and anal glands (Stein et al, 1982), ductal cells of the normal pancreas and normal salivary glands. PSA immunoreactivity is also seen in urethral and periurethral gland adenocarcinoma, extramammary Paget's disease of the penis and pleomorphic adenoma and carcinoma of the salivary gland (Elgamal et al, 1996). Neutrophils and some neuroendocrine tumors also stain for PSA. Specificity is improved by using the monoclonal antibodies. We have had consistency of results with clone ER-PR8 from Dako when used with MW-induced retrieval.

References
•Bostwick DG 1994. Prostate-specific antigen. Current role in diagnostic pathology of prostatic cancer. American Journal of Clinical Pathology; 102 (suppl 1): S31-S37.

•Clements A, Mukhtar A 1994. Glandular kallikreins and prostate specific antigen are expressed in the human endometrium. Journal of Endocrinology and Metabolism; 78: 1536-1539.

•Diamandis EP, Yu H 1995. New biological functions of prostate-specific antigen? Journal of Clinical Endocrinology and Metabolism; 80: 1515-1516.

•Elgamal AA, Ectors NL, Sunardhi-Widyaputra S et al 1996. Detection of prostate specific antigen in pancreas and salivary glands: a potential impact on prostatic carcinoma overestimation. Journal of Urology; 156:464-468.

•Stein BS, Peterson RO, Vangore S, Kendall AR 1982. Immunoperoxidase localization of prostate specific antigen. American Journal of Surgical Pathology; 2: 553-557.

Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.

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