title: Clinical and molecular aspects of a pediatric metachronous adrenocortical tumor.
abstract: The occurrence of metachronous adrenocortical carcinoma has rarely been described. We report a case of a child with virilizing adrenocortical metachronous tumors that, despite several metastases, presented long-term survival (15 years). We analyzed in this tumor IGF2, IGF1R and FGFR4 gene expression, and evaluated the presence of p.R337H germline p53 mutation and somatic CTNNB1 mutation. IGF2 gene was over-expressed in both left (Weiss score 5) and right (Weiss 7) adrenocortical tumors. IGF1R expression levels were higher in the right adrenocortical tumor. FGFR4 over-expression was also detected in the right adrenocortical tumor. In addition, this patient harbors the germline p.R337H p53 mutation and loss of heterozygosity (LOH) was detected in the tumors. No somatic CTNNB1 mutations were found in both tumors. In conclusion, we demonstrated in this unusual case the over-expression of growth signaling pathways, which are molecular mechanisms previously related to adrenocortical tumorigenesis. Furthermore, the absence of somatic CTNNB1 mutations, which is a molecular marker of poor prognosis in adults, might be related to the long-term survival of this patient.
authors.affiliation: Endocrinology Development Unit, Division of Endocrinology, Department of Internal Medicine, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. lorenalima@usp.br
authors.forename: Lorena de Oliveira
authors.initials: Lde O
authors.lastname: Lima
authors.forename: Antonio Marcondes
authors.initials: AM
authors.lastname: Lerario
authors.forename: Guilherme Asmar
authors.initials: GA
authors.lastname: Alencar
authors.forename: Luciana Pinto
authors.initials: LP
authors.lastname: Brito
authors.forename: Madson Queiroz
authors.initials: MQ
authors.lastname: Almeida
authors.forename: Sorahia
authors.initials: S
authors.lastname: Domenice
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Maria Candida Barrison Villares
authors.initials: MC
authors.lastname: Fragoso
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000556:secondary; D002675:Child, Preschool; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D009361:Neoplasm Invasiveness; D011629:Puberty, Precocious / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D051176:beta Catenin