The molecular pathogenesis of adrenal tumours

GENERAL ASPECTS Adrenal tumours are rare endocrine disorders. Clini-cally they may be silent, being identified incidentally during routine procedures (Ross & Aron 1990), or more rarely they may harbour intrinsic aggressive-ness, leading to a poor prognosis and short survival rates (Luton et al. 1990). The precise pathogenesis and molecular basis of adrenal tumours are at present unknown, but an increasing number of reports have gradually expanded our knowledge of the mecha-nisms of adrenal tumorigenesis. It has been recognised that many human cancers result from multiple and sequential genetic defects, rather than from a single molecular error, in a multi-step, cascade-like effect, the paradigm being that for colon cancer (Fearon & Vogelstein 1990). It is reasonable to believe that other human malignancies may follow this model, and, in fact, multiple defects have been identified in various other cancers, including those of endocrine organs such as thyroid tumours (Fagin et al. 1993). Endocrine tumours very often represent unique models of cancer; they are not normally recognised by their intrinsic biological aggressiveness, unlike other tumours, but rather as the excessive growth of an endocrine tissue, which retains its relatively normal functional capacity most of the time (Bravo & Gifford 1984, Freeman 1986). There are exceptions to this mie, represented by both medullary and (particularly) cortical adrenal tumours, which may develop highly malignant behaviour. The commonly benign features of various endocrine tumours have led many researchers to look for molecular defects in genes related to the normal pathway of endocrine tissue development, as non-specific proto-oncogenes and tumour suppressor genes, usually found deranged in other malignancies, have been shown to be normal in the majority of the endocrine neoplasms examined (Yoshimoto ef al. 1993, Reincke ef al. 1994, Dahia ef al. 1995). Certainly the identification of molecular defects in such tumours will help in the delineation of novel diagnostic and therapeutic approaches to these disorders in the future