Detection of disseminated prostate cells by reverse transcription- polymerase chain reaction (RT-PCR): Technical and clinical aspects

Abstract

The vital question of whether detection of extra-prostatic prostate cells by RT-PCR will prove to be clinically valuable is not readily answered; instead it resolves itself into many distinct issues, which depend on the target message or messages, various aspects of the procedures being used and the nature of the medical decision for which the information is needed. While the data included herein represent a collation and reduction of the large volume of results available, despite the amount of effort that has been expended, there are as yet few firm generalizations that can be safely drawn about the clinical utility of RT-PCR in prostate cancer. However, the large number of studies has been of definite value in this difficult field in illuminating important trends and suggesting the most fruitful paths for future studies and assay development. Although negative data cannot be ignored, it is still entirely possible that the methods used by groups reporting the most favorable results will be successfully transferred to other laboratories and will prove to be clinically useful. It is clear from the published results that one of the most urgent needs in this field is standardization. Due to the wide variety of RT-PCR methods in use for detection of circulating cells and to the nature of RT-PCR as a non-linear amplification procedure, standardization is both a critical and a complex issue. Standards are required both in the immediate future, to allow inter- laboratory comparisons of procedures in search of the best methods, and to control performance at the individual clinical laboratory. Standardization of procedures alone is clearly insufficient to allow useful inter-laboratory comparisons, because RT-PCR partakes of the nature of 'chaotic' mathematical models, in which small changes in initial conditions lead to large effects on the results. A useful standard would therefore be one which allows comparison of the results of the procedures. While the clinical utility of detection of extra-prostatic prostate cells by RT-PCR is still being determined, the value of the method in research is beyond question. Among the numerous issues that can be fruitfully addressed are the sites and routes of metastasis, phenotypic alterations associated with both adaptation to metastatic sites and subsequent growth, and, when quantitative methods are developed and optimized, the kinetics of metastasis and the prediction of outcomes based on a 'fingerprint' of prostate-cell phenotypic distribution. Quantification may also allow study of changes related to metastasis involving multiple genes, leading perhaps to the use of ratios of expression of affected genes as the most accurate and informative data representing these changes. This holds the promise of improving diagnostic procedures and treatment decisions.