Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients

• Published in: European journal of endocrinology Vol. 166; no. 1; pp. 61 - 67
• Main Authors: Fragoso, Maria Candida B V, Almeida, Madson Queiroz, Mazzuco, Tania L, Mariani, Beatriz M P, Brito, Luciana P, Gonçalves, Talita Cardoso, Alencar, Guilherme A, Lima, Lorena de O, Faria, Andre M, Bourdeau, Isabelle, Lucon, Antonio M, Freire, Daniel S, Latronico, Ana Claudia, Mendonca, Berenice B, Lacroix, Andre, Lerario, Antonio M
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01-01-2012
• Subjects: Adolescent; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - metabolism; Biological and medical sciences; Biomarkers, Tumor - metabolism; Brazil; Child; Child, Preschool; Clinical Study; Disease-Free Survival; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Humans; Infant; Infant, Newborn; Male; Medical sciences; Miscellaneous; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Protein Kinases - genetics; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Public health. Hygiene; Public health. Hygiene-occupational medicine; Vertebrates: endocrinology; South America; Brazil; America; Human; Prognosis; Adrenal cortex; Gene expression; Test validation; Cohort study; Adult; Evolution; Tumor; Predictive factor; Child; Endocrinology; Public health
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-11-0806

BackgroundA recent microarray study identified a set of genes whose combined expression patterns were predictive of poor outcome in a cohort of adult adrenocortical tumors (ACTs). The difference between the expression values measured by qRT-PCR of DLGAP5 and PINK1 genes was the best molecular predictor of recurrence and malignancy. Among the adrenocortical carcinomas, the combined expression of BUB1B and PINK1 genes was the most reliable predictor of overall survival. The prognostic and molecular heterogeneity of ACTs raises the need to study the applicability of these molecular markers in other cohorts.ObjectiveTo validate the combined expression of BUB1B, DLGAP5, and PINK1 as outcome predictor in ACTs from a Brazilian cohort of adult and pediatric patients.Patients and methodsBUB1B, DLGAP5, and PINK1 expression was assessed by quantitative PCR in 53 ACTs from 52 patients – 24 pediatric and 28 adults (one pediatric patient presented a bilateral asynchronous ACT).ResultsDLGAP5–PINK1 and BUB1B–PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. In the pediatric cohort, these molecular predictors were only marginally associated with disease-free survival but not with overall survival.ConclusionThis study confirms the prognostic value of the combined expression of BUB1B, DLGAP5, and PINK1 genes in a Brazilian group of adult ACTs. Among pediatric ACTs, other molecular predictors of outcome are required.