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Influence of the fibroblast growth factor receptor 4 expression and the G388R functional polymorphism on Cushing's disease outcome.
MedLine Citation:
PMID:  20660043     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
CONTEXT: Abnormal FGFR4 expression has been detected in pituitary tumors, especially in larger and invasive adenomas. In addition, the FGFR4 functional polymorphism G388R has been associated with poor outcome in several human malignancies. Then, we hypothesized that FGFR4 expression and genotype could be markers of adverse outcome of Cushing's disease after transsphenoidal surgery. OBJECTIVES: The objective was to investigate whether there is an association between the postoperative outcome of Cushing's disease (remission/recurrence) and the FGFR4 G388R genotype or the FGFR4 expression in corticotrophinomas. DESIGN AND PATIENTS: Clinical, hormonal, and pathological data of 76 patients who underwent the first transsphenoidal surgery were retrospectively reviewed. All patients were genotyped for G388R polymorphism. FGFR4 expression was assessed by real-time PCR in 18 corticotrophinomas. MAIN OUTCOME MEASURES: The outcome measures included the FGFR4 G388R genotype and FGFR4 expression in postoperative remission and recurrence of Cushing's disease. RESULTS: Homozygosis for FGFR4 glycine (Gly(388)) allele was associated with reduced disease-free survival, in the univariate analysis (hazard ratio of 6.91; 95% confidence interval of 1.14-11.26; P = 0.028). Male gender (P = 0.036), lack of pathology confirmation (P = 0.009), and cortisol levels more than 2 μg/dl in the early postoperative period (P < 0.001) were also significant predictors of Cushing's disease recurrence in the univariate analysis. FGFR4 overexpression was found in 44% of the corticotrophinomas, and it was associated with lower postoperative remission rate (P = 0.009). CONCLUSIONS: Our data suggest that homozygosis for FGFR4 Gly(388) allele and FGFR4 overexpression are associated with higher frequency of postoperative recurrence and persistence of Cushing's disease, respectively.
Authors:
Luciana Pinto Brito; Antonio Marcondes Lerário; Marcello Delano Bronstein; Iberê Cauduro Soares; Berenice Bilharinho Mendonca; Maria Candida Barisson Villares Fragoso
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-21
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E271-9     Citation Subset:  AIM; IM    
Affiliation:
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil. lucpbrito@gmail.com
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