Most adrenocortical
tumors are benign, unilateral,
adrenocortical adenomas that are often discovered incidentally.
Adrenocortical cancer is rare. Exceptionally, adrenocortical
tumors can be bilateral. Although most adrenocortical
tumors occur sporadically, they may also feature in congenital and/or familial disease. The identification of germline genetic defects in familial diseases associated with adrenocortical
tumors helped to define the somatic alterations in sporadic disease: for example, overexpression of
insulin-like growth factor 2 and alterations at the 11p15 locus (observed in
Beckwith-Wiedemann syndrome) are also found in most
adrenocortical cancers. Similarly, inactivating mutations of the TP53 gene, located at 17p13 (observed in
Li-Fraumeni syndrome), can also be found at the somatic level in sporadic
adrenocortical cancers, as can 17p13 allelic losses. Components of the
cyclic AMP signaling pathway--for example,
adrenocorticotropic hormone receptors and other membrane receptors, Gs
proteins and
protein kinase A--can be altered to various degrees in adrenocortical
tumors. More recently, gene profiling and genetic studies have shown that the Wnt-beta-catenin signaling pathway is frequently activated in adrenocortical
tumors. These research findings already have profound implications for clinical management of patients with adrenocortical
tumors, for example in unraveling the genetic origin of the disease in some patients, and in the development of molecular markers for diagnosis and prognosis. The new findings should also help in the development of new therapeutic options.