Molecular pathology and future developments.

There has already been a 'molecular' revolution in pathology. Demonstrating transcription of specific single genes or small gene sets and their protein products by in situ hybridisation and immunocytochemistry is routine in diagnostic and experimental pathology. A perhaps-greater revolution is imminent with the application of more recently established and emergent technologies in pathology. These include new approaches to polymerase chain reaction (PCR); simultaneous studies of multiple genes and their expression using oligonucleotide and cDNA arrays; serial analysis of gene expression (SAGE); expressed sequence tag (EST) sequencing, subtractive cloning and differential display; high-throughput sequencing; comparative genomic hybridization, multiplex fluorescence in situ hybridisation (FISH) (spectral karyotyping); reverse chromosome painting; knockout and transgenic organisms; laser microdissection and micro-machining; and new methods in bio-informatics, 'data mining' and data visualisation. Molecular methods will profoundly change diagnosis, prognosis and treatment targeting in oncology and elucidate fundamental mechanisms of neoplastic transformation. Individual susceptibility to specific diseases will become assessable and screening will be refined. The new molecular biology will be most fruitful in partnership with classical approaches to pathology: the expectation that molecular methods alone will answer all pathological questions is unrealistic. A further challenge for the biomedical community in the 'genome era' will be to ensure that the benefits of these sophisticated technologies are enjoyed globally.