Reverse transcriptase polymerase chain reaction for prostate specific antigen in the management of prostate cancer

Purpose: Polymerase chain reaction is a powerful tool for expanding minute quantities of deoxyribonucleic acid (DNA) for detailed study. Reverse transcriptase polymerase chain reaction (RT-PCR) involves the initial conversion of messenger ribonucleic acid (mRNA) to DNA, followed by the amplification of the DNA product for molecular analysis. The mRNA for prostate specific antigen (PSA) is expressed only by prostatic cells. RT-PCR offers a potentially more sensitive assay for the detection of cells expressing PSA mRNA in peripheral circulation or in extraprostatic tissues. The current status of RT-PCR in the amplification and detection of PSA gene expression in the management of prostate cancer 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 cell expressing PSA among 10 to 100 million lymphocytes can be detected by the RT-PCR assay. This assay may detect extraprostatic or circulating prostatic cells in peripheral blood, lymph nodes and bone marrow in many patients with prostate cancer. Various studies have reported sensitivities of detection of PSA expressing cells in the peripheral blood ranging from 0 to 88%. This wide range in the sensitivity may be partly due to tremendous variation between the protocols used in each study. In patients with lymph node metastasis the RT-PCR assay appears more reliable than immunohistochemistry for identification of prostatic tissue in the lymph node. In some series analyses of radical prostatectomy specimens suggest a strong correlation between a positive RT-PCR result 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 PSA expression in prostate cancer patients, and negative for detection in men with benign prostatic hyperplasia and in women. Sources of potential false-positive and false-negative results of this assay are identified and discussed. Conclusions: RT-PCR can detect PSA expressing cells that are otherwise undetectable by other means in patients with localized and metastatic cancers, This assay is highly specific, since PSA expressing cells were consistently undetectable in the peripheral circulation of patients without prostate cancer in most studies. Limited data to date suggest that this test may have a role in the staging of tumors before radical prostatectomy and in the serial followup of patients 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 behavior 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.