title: Association ofFOXM1expression with tumor histology and prognosis in Wilms tumor: Potential for a new prognostic marker.
abstract: Wilms tumor (WT) is the most common pediatric renal malignancy. A recent ontogenic model suggests that undifferentiated tumor state, and hence poor prognosis, in WT is determined by stabilization of β-catenin in the nucleus. Forkhead box M1 (FOXM1) is a downstream component of the Wnt pathway and promotes nuclear localization of β-catenin. As elevation ofFOXM1gene expression is prognostic in various types of malignancy, we hypothesized that highFOXM1expression in WT is associated with undifferentiated histology and thus poor prognosis. In the current study, the expression ofFOXM1mRNA was determined in 46 WT specimens and 11 renal tissue controls from patients undergoing tumor nephrectomy, and these data were assessed with regard to clinicopathological parameters. The results demonstrated an upregulation ofFOXM1in WT by 10-fold compared to normal tissue. Expression differed significantly between controls and tumors of intermediate- and high-risk histopathology (P<0.001, Kruskal-Wallis), and distinguished normal tissue from tumors of good and adverse clinical outcome (P<0.001, Kruskal-Wallis). Notably,FOXM1expression was significantly lower (P=0.009) in patients that received preoperative doxorubicin. These results suggest thatFOXM1may serve as a companion diagnostic factor for doxorubicin-based therapies in WT.
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, 80337 Bavaria, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Apelt
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, 80337 Bavaria, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hubertus
authors.affiliation: Institute of Pathology, Ludwig Maximilian University of Munich, Munich, 80337 Bavaria, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Saarland, Homburg, 66421 Saarland, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Saarland, Homburg, 66421 Saarland, Germany.
authors.forename: Rhoikos
authors.initials: R
authors.lastname: Furtwängler
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, 80337 Bavaria, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Von Schweinitz
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, 80337 Bavaria, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Kappler
keywords: FOXM1; Wilms tumor; forkhead box; nephroblastoma; prognosis