HOXA9 OVEREXPRESSION IN ADRENOCORTICAL CANCER

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 1-36-Adrenal Incidentaloma & Carcinoma
Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-25
Danilo Bacic*1, Andre Murad Faria2, Gabriela R V Sousa1, Beatriz Marinho Mariani3, Antonio Marcondes Lerario4, Maria Claudia N Zerbini5, Berenice Bilharinho Mendonca6, Maria Candida Barisson Villares Fragoso7, Ana Claudia Latronico8 and Madson Q Almeida9
1Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, 2Univ of Sao Paulo Medical School, Sao Paulo, SP, Brazil, 3Hospital das Clinicas, Sao Paulo, Brazil, 4Hosp das Clinicas, Sao Paulo, Brazil, 5Faculdade de Medicina da Universidade de São Paulo, 6Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 7Hosp Das Clinicas- FMUSP, Sao Paulo SP, Brazil, 8University of Sao Paulo, Sao Paulo-SP, Brazil, 9University of Sao Paulo, Sao Paulo, Brazil
Introduction: Previous studies from ours and other cohorts demonstrated that an increased expression of IGF2 and its receptor (IGF1R) has important role in the malignant phenotype of adult and pediatric adrenocortical tumors, respectively. HOX genes, a highly conserved subgroup of the homeobox superfamily, are related to the normal spatiotemporal embryogenesis of organs and limbs, regulating numerous processes including apoptosis, receptor signaling, differentiation, motility and angiogenesis. Aberrations in HOX gene expression have been reported in abnormal development and malignancy. Overexpression of the homeobox A9 (HOXA9) gene in B-lineage leukemia cells increases IGF1R expression and induces cell proliferation. Based on this recent evidence, we investigate in this study the HOXA9 gene expression in pediatric and adult adrenocortical tumors. Patients and methods: HOXA9 gene expression was assessed in 62 adrenocortical tumors from 18 children (14 adenomas and 4 carcinomas) and 44 adults (25 adenomas and 19 carcinomas) by quantitative real-time PCR using a relative quantification method. Data is presented as fold change in comparison to a commercial pool of normal adrenal cortex. Results: HOXA9 expression in adrenocortical tumors was 4.1 ± 1.9 (range, from 0 to 96) in comparison with the normal adrenal cortex. HOXA9 overexpression was significantly more frequent in pediatric adrenocortical tumors (44%, 8 out of 18) when compared to adult tumors (14%, 6 out of 44; X2= 5.97, p= 0.01). HOXA9 expression did not correlate with IGF1R and IGF2 mRNA concentrations in both children and adults with adrenocortical tumors. In the survival analysis, HOXA9 overexpression was associated with a reduced overall survival in adults with adrenocortical cancer (p= 0.03), but not with disease-free survival. On the other hand, HOXA9 overexpression was a not a predictor of prognosis in pediatric adrenocortical tumors. Conclusion: HOXA9 overexpression was more frequent in pediatric adrenocortical tumors, but it did not correlate with prognosis in children. Interestingly, HOXA9 overexpression was associated with a reduced overall survival in adults with adrenocortical cancer.

Nothing to Disclose: DB, AMF, GRVS, BMM, AML, MCNZ, BBM, MCBVF, ACL, MQA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Support: CNPq (470631/2012-0)