Expression of the lipogenic enzyme fatty acid synthase (FAS) as a predictor of poor outcome in nephroblastoma: an interinstitutional study.
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.


METHODS
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.
Camassei
Francesca Diomedi
FD
Department of Pathology, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy.
Jenkner
Alessandro
A
Ravà
Lucilla
L
Bosman
Cesare
C
Francalanci
Paola
P
Donfrancesco
Alberto
A
Alò
Piero L
PL
Boldrini
Renata
R
D000293:Adolescent; D014408:Biomarkers, Tumor; D002648:Child; D002675:Child, Preschool; D064429:Fatty Acid Synthases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D009396:Wilms Tumor / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D064429:Fatty Acid Synthases