MOLECULAR-BIOLOGY OF HUMAN PITUITARY-ADENOMAS

While the majority of pituitary tumours will remain benign, a proporti on will show invasive behaviour and a still smaller proportion will be come malignant. Recent studies at both the biochemical and molecular l evel are now defining the changes associated with pituitary tumour ini tiation and progression. Ln particular, the use of microsatellite anal ysis in determining regions of gene deletion has considerably advanced our understanding of pituitary tumourigenenesis. Bringing together th e data of several groups now allows a tentative map to be drawn showin g loss of heterozygosity at several chromosomal loci to be associated with the transition to the invasive and malignant phenotype, while cha nges associated with chromosome 9p and silencing, through methylation, of the tumour suppressor gene p16 appear to occur early in pituitary tumourigenesis. At the biochemical level, immunohistochemical studies have defined changes in key regulatory proteins along this multistep p athway. To determine whether these changes are truly predictive of tum our behaviour awaits carefully designed prospective studies. These fut ure studies may well aid decision-making regarding management in a man ner not possible using current histological assessment.