The molecular technologies of polymerase chain reaction (PCR) and reverse transcriptase–PCR (RT-PCR) are powerful tools for investigative medicine. These methods are being adapted increasingly for practical use in the clinical monitoring of patients with malignancy. As early as 1988, PCR alone was used in the detection of residual disease in patients treated for hematologic malignancies.<sup>21 Fey M.F., Kulozik A.E., Hansen-Hagge T.E. , e al. The polymerase chain reaction: A new tool for the detection of minimal residual disease in hematologic malignancies Eur J Cancer 1991 ;  27 : 89

Cliccare qui per andare alla sezione Riferimenti, 34 Lee M.S., Chang K.S., Cabanillas F. , e al. Detection of minimal residual cells carrying the t(14:18) by DNA sequence amplification Science 1988 ;  237 : 175

Cliccare qui per andare alla sezione Riferimenti, 37 Miyomura M., Tanimoto Y., Morishima K. , e al. Detection of philadelphia chromosome-positive acute lymphoblastic leukemias by polymerase chain reaction: Possible eradication of minimal residual disease by marrow transplantation Blood 1992 ;  79 : 1366

Cliccare qui per andare alla sezione Riferimenti, 65 Tycko B., Palmer J.D., Link M.P. , e al. Polymerase chain reaction amplification of rearranged antigen receptor genes using junction-specific oligonucleotides: Possible application for detection of minimal residual disease in acute lymphoblastic leukemia Cancer Cells 1989 ;  7 : 47

Cliccare qui per andare alla sezione Riferimenti</sup> In these situations, the tumor cells are identifiable because they have an abnormally rearranged or mutated gene that is not present in normal cells. Therefore direct PCR amplification of genomic DNA from the genetic region involved in tumorigenesis can identify the presence of the abnormal DNA even if the tumor cells are greatly diluted in a population of normal cells. The additional step of reverse-transcribing cellular messenger RNA (mRNA) to complementary DNA (cDNA) in RT-PCR enables the detection of tissue-specific cell markers in cell populations without the need for a specific mutation or gene rearrangement in the tumor cell. The availability of cell-specific markers for prostate (and prostate cancer) cells has enabled the recent rapid development of RT-PCR techniques that can detect the dissemination of prostate cancer cells to metastatic sites in prostate cancer patients.<sup>13 Dotta Y.H., Adams P.T., Drobyski W.R. , e al. Sensitive detection of occult breast cancer by the reverse transcriptase-polymerase chain reaction J Clin Onc 1994 ;  12 : 475

Cliccare qui per andare alla sezione Riferimenti, 34 Lee M.S., Chang K.S., Cabanillas F. , e al. Detection of minimal residual cells carrying the t(14:18) by DNA sequence amplification Science 1988 ;  237 : 175

Cliccare qui per andare alla sezione Riferimenti, 42 Moss T.J., Sanders D.G. Detection of neuroblastoma cells in blood J Clin Oncol 1990 ;  8 : 736

Cliccare qui per andare alla sezione Riferimenti, 44 Naito H., Kuzumaki N., Uchino J. , e al. Detection of tyrosine hydroxylase mRNA and minimal neorublastoma cells by the reverse transcription-polymerase chain reaction Eur J Cancer 1991 ;  27 : 762

Cliccare qui per andare alla sezione Riferimenti, 60 Smith B., Selby P., Southgate J. , e al. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction Lancet 1991 ;  338 : 1227  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> As early as 1990, Vessella and coworkers<sup>66 Vessella R.L., Blouke K.A., Stray J.E. , e al. The use of the polymerase chain reaction to detect metastatic prostate cancer in lymph nodes and bone marrow Proceedings of the American Association for Cancer Research 1992 ;  33 : 2367

Cliccare qui per andare alla sezione Riferimenti</sup> reported on the detection of prostate cells by RT-PCR for prostate-specific antigen (PSA) in lymph nodes and bone marrow samples of patients with metastatic prostate cancer. In 1992, Moreno et al<sup>39 Moreno J.G., Croce C.M., Fischer R. , e al. Detection of hematogenous micrometastasis in patients with prostate cancer Cancer Res 1992 ;  52 : 6110

Cliccare qui per andare alla sezione Riferimenti</sup> used RT-PCR to detect the presence of PSA mRNA in peripheral blood specimens of patients with metastatic prostate cancer. Since then, there have been numerous reports using this technology to detect the presence of occult prostate cells in blood, lymph nodes and bone marrow of patients with prostate cancer, and there is increasing evidence that this molecular assay provides clinically relevant information that can be used to improve treatment for patients with prostate cancer.

The aim of this article is to summarize the literature relating to these studies. In particular, the article focuses on specific areas including a review of RT-PCR technology; what problems are inherent in PCR-based technology, especially regarding its use in clinical assays; which prostate-specific marker might be used for these assays; how tissues compare for detection of prostate-specific markers; and what are the areas of consensus as well as those of continued controversy in the clinical application of this assay.