Identification of circulating prostate cancer cells: a challenge to the clinical implementation of molecular biology (review).

Conventional diagnosis of prostate cancer does not appear to be sensitive enough to differentiate pre-operatively between organ-confined and extracapsular disease. New technologies, arising from the field of molecular biology, have been introduced to improve diagnosis and their implementation into the clinical practice is nowadays extensively explored. In 1992, focusing on prostate cancer, the application of the highly sensitive and specific reverse transcription-polymerase chain reaction (RT-PCR) technology which amplifies predefined mRNA species was introduced. Assuming haematogenous prostate tissue-specific mRNA species to be representative for the presence of circulating prostate cancer cells, an impressive series of clinical studies, for the greater part addressing mRNA encoding for prostate-specific antigen (PSA), were performed to improve pre-operative staging (molecular staging) and prognosis of prostate cancer, and to study iatrogenic cell dissemination. In this review we summarize the efforts, concentrating on the RT-PCR methodology, to identify extracapsular prostate cancer cells in easy accessible body fluids. The substantial amount of available biological and clinical data allow an in depth illustration of the advantages, disadvantages and clinical future of this technology. The intrinsic limitations of the technology, technical as well as biological, will be addressed since these may well explain the controversies associated with its general acceptance in the clinical practice. Together with considerable improvements of the methodology to be expected in the near future, new avenues for the detection of disseminated prostate cancer cells will be subject of discussion.