The role of the ACTH receptor in adrenal tumors: Identification of a novel microsatellite marker

In vitro, the growth inhibiting effect of ACTH on adrenocortical cells is well documented, even though there are reports of opposite effects under defined cell culture conditions. In vivo, activation of the ACTH receptor (ACTHR) has a trophic effect on the adrenal cortex, while the effects on proliferation are still under discussion, especially since other POMC derived peptides have been characterized. However, ACTH is thought to act as a differentiation factor with inhibiting effects on tumor growth. In undifferentiated adrenocortical carcinomas, ACTHR expression is frequently lost, which is associated with extensive tumor growth. We describe a new microsatellite marker within the intron of the ACTHR gene termed ACTHRint1. In a series of 114 patients with various adrenal and non-adrenal tumors, the rate of heterozygosity was 100%. Only one out of 57 patients with adrenocortical adenoma showed LOH at the ACTHR locus, whereas 4 of 10 carcinomas had loss of one allele. Patients suffering from tumors with LOH showed a more aggressive disease course and had earlier recurrences with poor prognosis. These data confirm earlier findings that adrenocortical carcinomas frequently show loss of ACTHR expression, which is associated with a more aggressive tumor growth. However, whether the ACTHR is directly involved in tumor growth or acts a marker of differentiation that is lost in more advanced tumor stages is still not clear.