REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION FOR PROSTATE-SPECIFICANTIGEN IN THE MANAGEMENT OF PROSTATE-CANCER

Purpose: Polymerase chain reaction is a powerful tool for expanding mi nute quantities of deoxyribonucleic acid (DNA) for detailed study. Rev erse transcriptase polymerase chain reaction (RT-PCR) involves the ini tial conversion of messenger ribonucleic acid (mRNA) to DNA, followed by the amplification of the DNA product for molecular analysis. The mR NA for prostate specific antigen (PSA) is expressed only by prostatic cells. RT-PCR offers a potentially more sensitive assay for the detect ion of cells expressing PSA mRNA in peripheral circulation or in extra prostatic tissues. The current status of RT-PCR in the amplification a nd detection of PSA gene expression in the management of prostate canc er is reviewed. Materials and Methods: The literature was reviewed for available data using RT-PCR for detection of prostatic cells outside of the prostate. Results: Amplification of mRNA by RT-PCR represents a highly sensitive method of detection of gene expression. A single cel l expressing PSA among 10 to 100 million lymphocytes can be detected b y the RT-PCR assay. This assay may detect extraprostatic or circulatin g prostatic cells in peripheral blood, lymph nodes and bone marrow in many patients with prostate cancer. Various studies have reported sens itivities of detection of PSA expressing cells in the peripheral blood ranging from 0 to 88%. This wide range in the sensitivity may be part ly due to tremendous variation between the protocols used in each stud y. In patients with lymph node metastasis the RT-PCR assay appears mor e reliable than immunohistochemistry for identification of prostatic t issue in the lymph node. In some series analyses of radical prostatect omy specimens suggest a strong correlation between a positive RT-PCR r esult and capsular invasion by the tumor, while others do not support its use in determining pathological stage. In the majority of reports the RT-PCR assay was highly specific for detection of extraprostatic P SA expression in prostate cancer patients, and negative for detection in men with benign prostatic hyperplasia and in women. Sources of pote ntial false-positive and false-negative results of this assay are iden tified and discussed. Conclusions: RT-PCR can detect PSA expressing ce lls that are otherwise undetectable by other means in patients with lo calized and metastatic cancers, This assay is highly specific, since P SA expressing cells were consistently undetectable in the peripheral c irculation of patients without prostate cancer in most studies. Limite d data to date suggest that this test may have a role in the staging o f tumors before radical prostatectomy and in the serial followup of pa tients after treatment. RT-PCR may improve the detectability of lymph node metastasis over immunohistochemistry. Presently this test should remain a powerful research tool in the study of the biology and behavi or of prostate cancer, and it should not be used to guide any clinical decision making. The use of this assay as a prognostic and management tool for prostate cancer is in the earliest stages.