Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma
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Gabriela Resende Vieira de Sousa1, Tamaya C. Ribeiro1, Andre M. Faria1, Beatriz M.P. Mariani1, Antonio M. Lerario1,2, Maria Claudia N. Zerbini3, Iberê C. Soares1, Alda Wakamatsu3, Venancio A.F. Alves2,3, Berenice B. Mendonca1, Maria Candida B.V. Fragoso1,2, Ana Claudia Latronico1, Madson Q. Almeida1,2
1Unidade de Suprarrenal, Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
2Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
3Laboratório de Patologia Hepática LIM14, Divisão de Anatomia Patológica, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
Madson Q. Almeida, e-mail: [email protected]
Keywords: DICER1, TARBP2, miRNA, adrenocortical carcinoma, recurrence
Received: April 25, 2015 Accepted: May 30, 2015 Published: June 11, 2015
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.
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