Prostate-Specific Antigen and New Related Markers for Prostate Cancer

Abstract

Although prostate-specific antigen (PSA), or human kallikrein 3, is the most valuable tool available for the diagnosis and management of prostate cancer, as currently used it is insufficiently sensitive and specific for early detection or staging of the malignancy. Many new concepts have been introduced in order to optimize the clinical use of PSA measurements, but each one has its own drawbacks. The molecular forms of PSA, especially the free PSA, seem to be useful for the detection of prostate cancer in men with PSA concentrations falling in the 4-10 microg/l range. New molecular techniques, such as reverse transcriptase polymerase chain reaction for the detection of minimal amounts of PSA messenger RNA and prostate-specific membrane antigen, offer new promise for the prognosis and possibly staging of prostate cancer. On the other hand, human kallikrein 2, a serine protease closely related to PSA that is also expressed predominantly in the prostate, may be a new adjuvant marker for prostate cancer. As for its biological functions, PSA can no longer be regarded as a specific prostate molecule associated mainly with semen liquefaction when it has a possible role as a prognostic indicator in female breast cancer. The biological role of PSA in normal tissues and tumors may be much more complex than previously thought and requires further investigation.

Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas

“…Consistent with the report from Hirano et al [8], we find stronger napsin expression in highly and intermediately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas. The analysis of the titer of napsin A in the serum could be of use in lung cancer diagnosis, in the same manner as analyses of the serine proteases human glandular kallikrein 2 (hK2) and prostate specific antigen (PSA or hK3) are for evaluation of prostate cancer disease progression [16]. Both proteases are highly expressed in normal prostate tissue and in prostate cancer.…”

Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera

“…PSA is currently a well-established clinical marker as an indicator for prostate cancer (Daher and Beaini, 1998), with the advantages that it is secreted and enters the circulatory system, and that virtually all primary prostate tumors maintain PSA expression. Increasing levels of PSA in peripheral blood has been shown to be an effective clinical marker useful in detecting the presence of prostate cancer, either in the initial diagnosis or in the detection of disease progression following procedures such as radical prostatectomy (Abi-Aad et al, 1992).…”

“…First, there is a high level of false positive tests due to PSA expression in benign prostatic hyperplasia that result in unnecessary biopsies. Second, PSA can fail as a marker for residual disease since not all metastases maintain expression of PSA (Daher and Beaini, 1998;Sissons et al, 1992), and the presence of the PSA gene by reverse transcription (RT) -PCR from blood does not unequivocally indicate specific prostatic metastases (Thiounn et al, 1997). Due to these limitations, additional markers for prostate cancer are needed.…”

Molecular aspects of prostate cancer: implications for future directions

“…New molecular techniques, such as RT-PCR (reverse transcription polymerase chain reaction) for the detection of minimum mRNA that codes for PSA and PMSA (membrane prostate specific antigen), offer new perspectives for the diagnosis, prognosis and possibly for PCa staging (31). Another limitation of PSA is that actually it is not really prostate specific, and a possible role as a prognostic indicator also in woman breast cancer has been described (32).…”