Prostate-specific antigen (PSA)

Characteristics

Prostate-specific antigen (PSA) is a single-chain 34-kd glycoprotein of 237 amino acids containing approximately 8% carbohydrate. It is a serine protease produced almost exclusively by prostatic epithelial cells. PSA has chymotrypsin-like, trypsin-like and esterase-like activity. From the epithelial cells of the prostate, PSA is secreted via the prostatic ductal system into seminal plasma, where it catalyses the liquefaction of the seminal coagulum after ejaculation. The PSA gene, , which belongs to the kallikrein gene family, is located on chromosome 19, region 13q.
With immunohistochemical techniques, PSA can be demonstrated uniformly in normal prostate in the secretory epithelial cells of prostatic acini (Fig 1A). The apical portion of the epithelial cell cytoplasm shows more intense staining than the lower part. Basal cells, transitional epithelium or stromal cells don not express PSA. Similarly, metaplastic squamous epithelium is negative for PSA.
PSA is highly specific for prostate glandular epithelium. A few normal tissues at extraprostatic sites do, however, express PSA. These include scattered cells in the prostatic urethra (Fig. 1B) and cloaca-derived tissues such as periurethral glands in males and females, anal glands and urachus. Seminal vesicles not express PSA. In the urinary bladder, no PSA is seen in urothelium or in von Brunn’s nests, whereas PSA immunoreactivity has been described in bladder epithelium in cystitis cystica and cystitis glandularis.

Neoplasms

PSA is readily demonstrated in adenocarcinomas of the prostate in about 99% of the cases (Figs. 2A-F). There is a correlation between malignancy grade and intensity of staining, high grade carcinomas displaying weaker expression (Fig. 2B). About 1% of poorly differentiated carcinomas have been negative for PSA. Radiation has not been shown to influence immunohistochemical PSA detection but reduction of staining intensity has been described following hormonal treatment. Different types of prostatic carcinoma, including ductal adenocarcinoma, mucinous, signet ring and small cell carcinoma, have been described to express PSA, whereas rare carcinoma with squamous differentiation as well as adenoid cystic carcinoma have been negative for PSA.
Prostatic adenocarcinomas metastatic to lymph nodes or bones are, equally to primary carcinoma, identifiable by staining for PSA (Figs. 2E-F).

PSA has been found in rare urethral papillomas (Fig. 2G) and in some extraprostatic neoplasms, such as female and male breast carcinoma, as well as salivary and sweat gland tumours.

Application

Due to the high specificity of PSA for prostatic glandular epithelium, it is very useful in identifying prostatic carcinoma in the prostate and in the adjacent organs often affected by epithelial malignancies, i.e. rectum and urinary bladder (Figs. 2C-D). Rectal adenocarcinoma, urothelial carcinoma or adenocarcinoma of the urinary bladder no not express PSA. Lack of PSA immunoreactivity in a very poorly differentiated malignancy does not, however, exclude the diagnosis of prostate cancer.
Differential diagnosis of metastasis, especially in lymph nodes or bone, with unknown primary malignancy is another useful application for PSA immunohistochemistry. Metastasis of a PSA-expressing male breast carcinoma or of a PSA negative prostate carcinoma are rare exceptions for usually easy identification of prostate carcinoma as the source of metastasis.

Visualization

mAbs ER-PR8, PSA-001,07, OS94.3, PSB535, 2009 and SC.5; pAbs (DakoCytomation). Staining of non-prostatic tissue is more frequently seen with pAbs indication some vross reaction with other kallikreins.
Recommended control tissue: Normal/hyperplastic prostate and high grade prostate adenocarcinoma with known weak PSA expression. A weak to moderate background reaction in the prostate stroma is acceptable. However,iit is also advisable to include non-prostatic tissue (e.g., appendix or tonsil) to verify the specificity.

Assessments

Run 12 2004

Selected references

Alanen KA, et al. Immunohistochemical labelling for prostate specific antigen in non-prostatic tissues. Pathol Res Pract 1996;192:233-237.
Bostwick DG. Prostate-apecific antigen. Current role in diagnostic pathology of prostate cancer. Am J Clin Pathol 1994;102(Suppl I):S31-S37.
Bostwick DG, et al. Immunohistochemistry of the prostate and bladder, testis and renal tumors. In: Dabbs DJ. Diagnostic Immunohistochemistry. Philadelphia, Churchill Livingstone, 2002:407-434.
DeMarzo AM, et al. Pathological and molecular aspects of prostate cancer. Lancet 2003,361:955-964.
Epstein JI. PSA and PAP as immunohistochemical markers in prostate cancer. Urol Clin N 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.
Lilja H. Biology of prostate-specific antigen. Urology 2003;62(Suppl 5A):27-33.
Millar EK, et al. Ductal (endometrioid) adenocarcinoma of the prostate: a clinicopathological study of 16 cases. Histopathology 1996;29:11-19.
Minei S, et al. Adenoid cystic carcinoma of the prostate: A case report with immunohistochemical an in situ hybridization for prostate-specific antigen. Int J Urol 2001;8:S41.
Parwani AV, et al. Prostate carcinoma with squamous differentiation: an analysis of 33 cases. Am J Surg Pathol 2004;28:651-657.
Yu H, Berkel H. Prostate-specific antigen (PSA) in women. J La State Med Soc 1999;151:209-213.