Clinical and molecular aspects of adrenocortical tumourigenesis.
Adrenal masses are a common problem affecting 3-7% of the population. The majority turn out to be benign adrenocortical adenomas, which may be functional or non-functional. Much more rarely, these masses represent a primary adrenal carcinoma. It is becoming increasingly recognized that of the benign functioning adenomas or hyperplasias, the majority will hypersecrete aldosterone and this will be more frequently detected when hypertensive populations are screened for this disease. In contrast, the incidence of primary adrenocortical carcinoma has remained steady and for this disease, surgery represents the mainstay of treatment. The advent of laparoscopic adrenal surgery has lowered the threshold size for recommending surgery for asymptomatic adrenal masses and as such, an increased proportion of adrenocortical cancers are being resected and detected at an earlier stage. Recent progress has been made in our understanding of the key genetic changes which underpin the biology of this disease. Progression from adrenal adenoma to carcinoma involves a monoclonal proliferation of cells which, among other defects, have undergone chromosomal duplication at the 11p15.5 locus leading to overexpression of the IGF2 gene and abrogation of expression of the CDKN1C and H19 genes. TP53 is involved in progression to carcinoma in a subset of patients and the frequency of ACTH receptor deletion needs to be more fully explored. Other key oncogenes and tumour suppressor genes remain to be identified although the chromosomal loci in which they lie can be identified at 17p, 1p, 2p16 and 11q13 for tumour suppressor genes and chromosomes 4, 5 and 12 for oncogenes.
Sidhu
Stan
S
University of Sydney Endocrine Surgical Unit and Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia. sidhu@med.usyd.edu
Gicquel
Christine
C
Bambach
Christopher P
CP
Campbell
Peter
P
Magarey
Christopher
C
Robinson
Bruce G
BG
Delbridge
Leigh W
LW
D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006929:Hyperaldosteronism / Q000209:etiology / Q000503:physiopathology; D011379:Prognosis; D018043:Receptors, Corticotropin / Q000502:physiology
D018043:Receptors, Corticotropin; D006854:Hydrocortisone