Pediatric and Adult Adrenocortical Tumor Display Different Patterns of SHH Pathway Expression

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

Poster Board MON-18
Debora Cristiane Gomes*1, Leticia Ferro Leal1, Livia Mara Mermejo1, Maria Candida Barisson Villares Fragoso2, Ana Claudia Latronico2, Carlos Scrideli1, Luis Gonzaga Tone1, Silvio Tucci1, Carlos Eduardo Martinelli1, Jose Andres Yunes3, Maria Jose Mastellaro3, Ana Luiza Seidinger3, Silvia Regina Brandalise3, Ayrton Custodio Moreira1, Leandra Naira Ramalho4, Margaret De Castro1 and Sonir Roberto Antonini1
1School of Medicine of Ribeirao Preto-University of Sao Paulo, Ribeirao Preto-SP, Brazil, 2University of Sao Paulo, Sao Paulo-SP, Brazil, 3Boldrini Children's Center, Campinas-SP, Brazil, 4School of Medicine of Ribeirao Preto - University of Sao Paulo, Ribeirao Preto-SP, Brazil
Background/Objectives: In animals, SHH pathway plays a role in adrenal development. Its involvement in adrenal tumorigenesis is unknown. We analyzed the involvement of the SHH pathway in adrenocortical tumors (ACT). Patients/Methods: Eighty-one ACT patients [61 children (79% female) and 20 adults (90% female)] were evaluated. Median age at diagnosis was 1.8 and 32.5 years, respectively.  All but 4 ACT were hormone-secreting tumors. Tumor staging – Pediatric: I=61%; II, III and IV= 13% each. Adult: I=25%, II=35%, III=15% and IV=25%. The common P53 p.R337H mutation was found in 85.2% and 20% of children and adults ACT, respectively. The mRNA expression of SHH, PTCH, SMO, GLI1, GLI2, GLI3 and SUFU genes was evaluated by qPCR. Normal adrenocortical tissues from 10 pediatric and 9 adult subjects were analyzed as controls for pediatric and adult ACT, respectively. Mann-Whitney test, linear regression models, Kaplan-Meier curves and Log Rank test were used. Results: SHH pathway genes were expressed in pediatric and adult normal adrenal tissues. Interestingly, the expression of the ligand SHH (p=0.01), receptors PTCH (p=0.01) and SMO (p=0.04) and mediators GLI1 (p=0.002), GLI2 (p=0.02) and GLI3 (p=0.01) was higher in adult adrenal control tissues than in pediatric ones. In childhood ACTs, most of SHH pathway genes were down regulated compared to controls, ACTs presented lower expression of SHH (95% CI= 1.22 to 4.22, p<0.01), PTCH (95% CI= 0.15 to 2.64, p=0.03), SMO (95% CI= 0.67 to 2.89, p<0.01), GLI1 (95% CI= 1.59 to 3.94, p<0.01) and GLI3 (95% CI= 0.31 to 2.31, p=0.01). Conversely, compared to controls adults, adult ACTs presented higher expression of PTCH (IC95%= -2,82 to -0,12; p=0,03), SMO (IC95%=-2,96 to -0,01; p=0,04), GLI3 (IC95%=-2,48 to -0,26; p=0,02), and SUFU (IC95%=-2,58 to -0,43; p<0,01). PTCH and SMO mRNA expression was lower in pediatric TACs with TP53 mutation than in TP53 wild type (95% CI= 0.27 to 2.94, p= 0.02 and 95% CI = 0.23 to 2.61, p= 0.02, respectively). In pediatric and adult ACT groups no associations were found between gene expression profile and outcome. Conclusions: In normal adrenal cortices, SHH pathway appears to be more active in adults than in children. Pediatric and adult ACTs also display different SHH pathway expression pattern. In adult ACTs SHH pathway is up-regulated and is down-regulated in pediatric ones. These data support a different involvement of the SHH pathway in adult and pediatric ACTs.


*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: Sao Paulo State Reserch Coundil (FAPESP) grant 11/13807-4 and CNPq.