Etiopatogênese Molecular dos Tumores Corticotróficos

Abstract

Molecular Etiopathogenesis of Corticotrophic Tumors.Corticotropinomas represent approximately 80% of the etiology of Cushing's syndrome in adults. In the past decade remarkable advances in the knowledge of the normal anterior pituitary development, in the pathogenesis of the pituitary tumors, as well as in the factors involved in the tumoral progression have been made. General principles of tumorigenesis are valid in corticotrophic tumors and it is clear that this is a multistep and multifactorial process, resulting from the interaction of initiating and promoting events. Most of the oncogenes and tumor suppressor genes related to other tumor types do not seem to contribute in this process, although abnormal expression of some of these genes, like PTTG, p53 and p16 can be related to a more aggressive phenotypic behavior. Investigation of the corticotrophicspecific regulatory pathways, mainly the structure and expression of the CRH, AVP, and GR receptor genes has also not shown significant abnormalities. However, it is possible that disruption in regulatory regions of these genes or in their transcription factors could be involved. Future studies in the regulatory mechanisms of both normal and tumoral corticotrophic cells could contribute in defining better