title: Correlation of tumor-associated macrophages and clinicopathological factors in Wilms tumor.
abstract: OBJECTIVE
  Despite high long-term survival rates in patients with Wilms tumor, there is a need to develop better prognostic biomarkers in order to maximize cure while avoiding treatment-associated morbidities. Tumor-associated macrophages have been recently associated with poorer prognosis and increased disease progression in a number of adult cancers. We investigated the relationship between macrophages and clinicopathological fators in this pediatric solid tumor.
  
  
  METHODS
  Tissue microarray sections of 124 Wilms tumor cases obtained from the Cooperative Human Tissue Network were stained with CD68, a macrophage marker using standard immunohistochemical techniques and quantified using digital image processing techniques. Macrophage densities were correlated by tumor stage, and survival analyses were conducted with available clinical data. Immunohistochemistry was performed on 25 additional Wilms tumor cases obtained from the tumor bank at Columbia University Medical Center and correlated with presence of tumor microvascular invasion.
  
  
  RESULTS
  Mean macrophage count densities in stage IV tumors were significantly greater than densities in stage I and III tumors (p=.021, .036). Although the overall and disease-free survival did not differ between high and low macrophage presence groups across all stages, increased macrophage presence was associated with decreased disease-free survival in patients with stage II tumors (p=0.035). Increased macrophage presence may have also correlated with decreased disease-free survival in stage IV patients, but the sample size was too small to allow detection of this difference with significance (p=0.575). Increased macrophage presence was associated with tumor microvascular invasion (p=0.0004).
  
  
  CONCLUSIONS
  Our results suggest that macrophage recruitment may be associated with disease progression in Wilms tumor. Quantitation of macrophage presence may therefore be a useful adjunct in refining staging algorithms for patients with stage II Wilms tumor. Such data might be useful in the effort to reduce the risk of adverse effects associated with under- or overtreatment of this neoplasm.
authors.affiliation: Division of Pediatric Surgery, Columbia University Medical Center, 3959 Broadway, CHN 214, New York, NY, 10032, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Liou
authors.affiliation: Division of Pediatric Surgery, Columbia University Medical Center, 3959 Broadway, CHN 214, New York, NY, 10032, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Bader
authors.affiliation: Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY, 10032, USA.
authors.forename: Antai
authors.initials: A
authors.lastname: Wang
authors.affiliation: Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Darrell
authors.initials: D
authors.lastname: Yamashiro
authors.affiliation: Division of Pediatric Surgery, Columbia University Medical Center, 3959 Broadway, CHN 214, New York, NY, 10032, USA.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Kandel