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Endocrinology

Abstract 3464: Prognostic value of DICER1 expression in adrenocortical cancer patients

Gabriela Resende V de Sousa, Tamaya C. Ribeiro, André M. Faria, Beatriz MP Mariani, Antonio M. Lerario, Ibere C. Soares, Maria Claudia N. Zerbini, Alda Wakamatsu, Venancio AF Alves, Berenice B. Mendonca, Maria Candida BV Fragoso, Ana Claudia Latronico and Madson Almeida
Gabriela Resende V de Sousa
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Tamaya C. Ribeiro
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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André M. Faria
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Beatriz MP Mariani
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Antonio M. Lerario
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Ibere C. Soares
Hospital do Câncer de Barretos, Porto Velho, Brazil;
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Maria Claudia N. Zerbini
Divisão de Anatomia Patológica, Hospital das Clínicas, Laboratório de Patologia Hepática LIM14, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Alda Wakamatsu
Divisão de Anatomia Patológica, Hospital das Clínicas, Laboratório de Patologia Hepática LIM14, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Venancio AF Alves
Divisão de Anatomia Patológica, Hospital das Clínicas, Laboratório de Patologia Hepática LIM14, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Berenice B. Mendonca
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Maria Candida BV Fragoso
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas & Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil.
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Ana Claudia Latronico
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil;
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Madson Almeida
Serviço de Endocrinologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas & Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil.
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DOI: 10.1158/1538-7445.AM2015-3464 Published August 2015
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Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract

Deregulation of microRNA (miRNA) expression in adrenocortical carcinomas (ACCs) has important prognostic and therapeutic implications. DICER1, an endoribonuclease in the RNase III family, is a key component of the miRNA processing machinery. In cooperation with its cofactor, transactivation response (TAR) RNA-binding protein (TRBP2), DICER1 cuts the pre-miRNA to meet the specification. Low DICER1 expression was associated with poor clinical outcome in ovarian, breast and lung cancer. Recently, DICER1 mutations in the RNase IIIb domain were found in steroidogenic Sertoli-Leydig cell and embryonic tumors. In this study, we assessed the mRNA and/or protein expression of DICER1 and TARBP2 in adult adrenocortical tumors (ACTs). Additionally, we investigated DICER1 and TARBP2 hot spot mutations. Expression of miRNAs (miR-103, miR-107 and miR-497) involved in DICER1 and TARBP2 regulation was also determined. DICER1 protein expression was analyzed in 151 adult ACTs (77 adenomas and 74 carcinomas). Messenger DICER1 and TARBP2 expression was assessed in 55 ACTs (30 adenomas and 25 carcinomas) by quantitative real-time PCR. Expression of miR-103, miR-107 and miR-497 was determined in the same cohort. In addition, we sequenced four metal-binding sites (codons 1709 and 1705 in exon 24; codons 1810 and 1813 in exon 25) within the RNase IIIb catalytic center of DICER1 gene, and the (C)5 coding microsatellite repeat of exon 5 of TARBP2 gene in 61 ACTs. Low DICER1 protein expression was significantly associated with reduced overall (p = 0.01) and disease-free survival (p = 0.01) in ACC patients. Among ACC patients with stage 3 or 4, 22 out of 32 (69%) displayed low DICER1 protein expression (X2 = 10.1, p = 0.01). DICER1 protein expression was not significantly different between adenomas and carcinomas. At mRNA level, DICER1 expression had an important superposition between adenomas and carcinomas, but it was higher in carcinomas than in adenomas [median (range); 1.96 (-1.4 to 4.54) vs. 0.81 (-1.5 to 99) respectively, p = 0.03]. Among ACC patients, DICER1 mRNA levels did not predict outcome. TARBP2 expression was not associated with histological and clinical parameters. In addition, expression of miR-103, miR-107 and miR-497 did not correlate with DICER1 and TARBP2 expression in ACTs. No variant was identified in the hot spot mutation region of DICER1 and TARBP2 genes. In conclusion, DICER1 expression was significantly associated with poor outcome in adult ACC patients. However, DICER1 deregulation in ACCs was not caused by mutations within the RNase IIIb domain and not associated with expression of its regulatory miRNAs.

Support: FAPESP (2012/21272-6; 2013/09621-8)

Note: This abstract was not presented at the meeting.

Citation Format: Gabriela Resende V de Sousa, Tamaya C. Ribeiro, André M. Faria, Beatriz MP Mariani, Antonio M. Lerario, Ibere C. Soares, Maria Claudia N. Zerbini, Alda Wakamatsu, Venancio AF Alves, Berenice B. Mendonca, Maria Candida BV Fragoso, Ana Claudia Latronico, Madson Almeida. Prognostic value of DICER1 expression in adrenocortical cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3464. doi:10.1158/1538-7445.AM2015-3464

  • ©2015 American Association for Cancer Research.
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Cancer Research: 75 (15 Supplement)
August 2015
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Abstract 3464: Prognostic value of DICER1 expression in adrenocortical cancer patients
Gabriela Resende V de Sousa, Tamaya C. Ribeiro, André M. Faria, Beatriz MP Mariani, Antonio M. Lerario, Ibere C. Soares, Maria Claudia N. Zerbini, Alda Wakamatsu, Venancio AF Alves, Berenice B. Mendonca, Maria Candida BV Fragoso, Ana Claudia Latronico and Madson Almeida
Cancer Res August 1 2015 (75) (15 Supplement) 3464; DOI: 10.1158/1538-7445.AM2015-3464

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Abstract 3464: Prognostic value of DICER1 expression in adrenocortical cancer patients
Gabriela Resende V de Sousa, Tamaya C. Ribeiro, André M. Faria, Beatriz MP Mariani, Antonio M. Lerario, Ibere C. Soares, Maria Claudia N. Zerbini, Alda Wakamatsu, Venancio AF Alves, Berenice B. Mendonca, Maria Candida BV Fragoso, Ana Claudia Latronico and Madson Almeida
Cancer Res August 1 2015 (75) (15 Supplement) 3464; DOI: 10.1158/1538-7445.AM2015-3464
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