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Publications (2)10.86 Total impact

  • Article: The role of fibroblast growth factor receptor 4 overexpression and gene amplification as prognostic markers in pediatric and adult adrenocortical tumors.
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    ABSTRACT: FGFR4 overexpression has been demonstrated in human neoplasms, including adrenocortical tumors (ACTs). However, the molecular mechanisms underlying FGFR4 upregulation and their influence in the outcome have not been fully addressed in ACTs. To evaluate FGFR4 expression in a Brazilian cohort of ACT patients and to verify if FGFR4 gene amplification is associated with overexpression. 57 tumors from 25 children and 32 adults (37 adenomas and 20 carcinomas) were studied. Gene expression was evaluated by qRT-PCR. Gene amplification was assessed by MLPA. In pediatric ACTs, FGFR4 transcripts were overexpressed in all except 3 cases (88%). In contrast, in adults, FGFR4 overexpression was detected in 47% of samples (15 out of 32) and was significantly higher in carcinomas [9.35 (0.21 - 35.73) vs. 1.44 (0.53 - 9.85), for carcinomas and adenomas, respectively; p=0.004)]. An increased FGFR4 copy number was identified in 8.3% (1 of 12) and 54.5% (6 of 11) of adult adenomas and carcinomas, respectively (p=0.027). In adults, FGFR4 overexpression and amplification were predictors of malignancy (p=0.049 and p=0.008, respectively). FGFR4 overexpression was demonstrated in both pediatric and adult ACTs suggesting an important role in adrenocortical tumorigenesis. In adults, FGFR4 overexpression was detected mainly in carcinomas and was associated with locus amplification in most cases.
    Endocrine Related Cancer 01/2012; 19(3):L11-3. · 4.36 Impact Factor
  • Article: Steroidogenic factor 1 overexpression and gene amplification are more frequent in adrenocortical tumors from children than from adults.
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    ABSTRACT: Background: Steroidogenic factor 1 (SF-1) is a key determinant of endocrine development and function of adrenal cortex. SF-1 overexpression and gene amplification were previously demonstrated in a small group of pediatric adrenocortical tumors. Objective: Our objective was to determine the frequency of SF-1 protein expression and gene amplification in a large cohort of pediatric and adult adrenocortical tumors. Patients: SF-1 protein expression was assessed in a cohort of 103 adrenocortical tumors from 36 children and 67 adults, whereas gene amplification was studied in 38 adrenocortical tumors (17 from children). Methods: Tissue microarray, multiplex ligation-dependent probe amplification, and quantitative real-time PCR were used. Results: A strong nuclear SF-1 expression was detected by tissue microarray in 56% (20 of 36) and 19% (13 of 67) of the pediatric and adult adrenocortical tumors, respectively (P = 0.0004). Increased SF-1 copy number was identified in 47% (eight of 17) and 10% (two of 21) of the pediatric and adult adrenocortical tumors, respectively (P = 0.02). All adrenocortical tumors with SF-1 gene amplification showed a strong SF-1 staining, whereas most of the tumors (61%) without SF-1 amplification displayed a weak or negative staining (P = 0.0008). Interestingly, a strong SF-1 staining was identified in five (29%) pediatric adrenocortical tumors without SF-1 amplification. The frequency of SF-1 overexpression and gene amplification was similar in adrenocortical adenomas and carcinomas. Conclusion: We demonstrated a higher frequency of SF-1 overexpression and gene amplification in pediatric than in adult adrenocortical tumors, suggesting an important role of SF-1 in pediatric adrenocortical tumorigenesis.
    The Journal of clinical endocrinology and metabolism 03/2010; 95(3):1458-62. · 6.50 Impact Factor