TY - JOUR
T1 - Expression of the lipogenic enzyme fatty acid synthase (FAS) as a predictor of poor outcome in nephroblastoma
T2 - An interinstitutional study
AU - Camassei, Francesca Diomedi
AU - Jenkner, Alessandro
AU - Ravà, Lucilla
AU - Bosman, Cesare
AU - Francalanci, Paola
AU - Donfrancesco, Alberto
AU - Alò, Piero L.
AU - Boldrini, Renata
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Background. Treatment of nephroblastoma (Wilms tumor) has presently achieved a greater than 80% cure rate. Pathologic stage and grade are considered the most reliable prognostic parameters, but other biologic factors are under study in order to improve patient stratification into risk groups. Correlation of elevated levels of the lipogenic enzyme fatty acid synthase (FAS) with aggressiveness of some cancers has drawn attention to this enzyme as a possible marker of poor prognosis. Procedure. To determine the predictive strength of FAS expression in Wilms tumor (with particular emphasis on intermediate risk, i.e., non anaplastic tumors, the vast majority of nephroblastomas), we evaluated immunostaining expression in archival specimens from 94 neoplasms. The degree of expression was correlated with stage, grade, clinical course and administration of prenephrectomy chemotherapy. Results. Expression of FAS increased in anaplastic tumors (P = 0.043) and higher stages (P = 0.029). FAS expression correlated with OS and DFS at both univariate and multivariate analysis. Comparable results were obtained when analyzing the intermediate risk population separately. Pretreatment resulted in an increased FAS expression, without reaching significance level (P = 0.059). Conclusions. Expression of FAS might be an independent prognostic factor, particularly for intermediate-risk patients. The blockade of fatty acid synthesis by inhibition of FAS enzymatic function by means of metabolic analogues might prove a novel target pathway for the treatment of nephroblastoma.
AB - Background. Treatment of nephroblastoma (Wilms tumor) has presently achieved a greater than 80% cure rate. Pathologic stage and grade are considered the most reliable prognostic parameters, but other biologic factors are under study in order to improve patient stratification into risk groups. Correlation of elevated levels of the lipogenic enzyme fatty acid synthase (FAS) with aggressiveness of some cancers has drawn attention to this enzyme as a possible marker of poor prognosis. Procedure. To determine the predictive strength of FAS expression in Wilms tumor (with particular emphasis on intermediate risk, i.e., non anaplastic tumors, the vast majority of nephroblastomas), we evaluated immunostaining expression in archival specimens from 94 neoplasms. The degree of expression was correlated with stage, grade, clinical course and administration of prenephrectomy chemotherapy. Results. Expression of FAS increased in anaplastic tumors (P = 0.043) and higher stages (P = 0.029). FAS expression correlated with OS and DFS at both univariate and multivariate analysis. Comparable results were obtained when analyzing the intermediate risk population separately. Pretreatment resulted in an increased FAS expression, without reaching significance level (P = 0.059). Conclusions. Expression of FAS might be an independent prognostic factor, particularly for intermediate-risk patients. The blockade of fatty acid synthesis by inhibition of FAS enzymatic function by means of metabolic analogues might prove a novel target pathway for the treatment of nephroblastoma.
KW - Fatty acid synthase
KW - Favorable histology
KW - Immunohistochemistry
KW - Nephroblastoma
KW - Prognosis
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U2 - 10.1002/mpo.10274
DO - 10.1002/mpo.10274
M3 - Article
C2 - 12652618
AN - SCOPUS:0037403024
VL - 40
SP - 302
EP - 308
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
SN - 1545-5009
IS - 5
ER -