Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma

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Vieira de Sousa, Gabriela Resende ^[1] ; Ribeiro, Tamaya C. ^[1] ; Faria, Andre M. ^[1] ; Mariani, Beatriz M. P. ^[1] ; Lerario, Antonio M. ^{[1, 2]} ; Zerbini, Maria Claudia N. ^[3] ; Soares, Ibere C. ^[1] ; Wakamatsu, Alda ^[3] ; Alves, Venancio A. F. ^{[3, 2]} ; Mendonca, Berenice B. ^[1] ; Fragoso, Maria Candida B. V. ^{[1, 2]} ; Latronico, Ana Claudia ^[1] ; Almeida, Madson Q. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Hormonios & Genet Mol LIM42, Div Endocrinol & Metabol, Fac Med, Unidade Suprarrenal, Endocrinol Desenvolvimento, Ho, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Lab Patol Hepat LIM14, Div Anat Patol, Hosp Clin, Fac Med, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 6, n. 26, p. 22724-22733, SEP 8 2015.
• Citações Web of Science: 7

Resumo

Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas. (AU)

• Processo FAPESP: 12/21272-6 - Análise do gene DICER1 em tumores adrenocorticais de crianças e adultos
• Beneficiário: Madson Queiroz Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Regular