Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted Wilms' tumor.
OBJECTIVE
The sera and urine of children with Wilms' tumor (WT) often contain increased concentrations of hyaluronan (HA). The authors developed a heterotransplant model to investigate whether serum HA concentrations could predict the histology and progression of WT.


METHODS
Random portions of 8 human WT specimens (7 favorable and 1 unfavorable histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SCID) mice. After 6 to 20 weeks of observation, animals were killed, and serum HA concentrations, tumor histology, and local invasion were determined.


RESULTS
Sera of mice supporting tumor growth had a median HA concentration of 9,379 microg/L (range, 459 to 3,206,176 microg/L) compared with a median HA concentration of 416 microg/L (range, 204 to 782 microg/L) in animals not supporting tumor growth. The highest serum HA concentrations were detected in animals harboring unfavorable histology blastemal-predominant tumors, whereas animals supporting favorable histology epithelial- and stromal-predominant tumors had the lowest serum HA concentrations. In association with markedly increased serum HA, undifferentiated blastemal tumors showed significantly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with invasive as compared with noninvasive tumors for each histological type. Complete resection of established tumors also resulted in the return of serum HA to preheterotransplant concentrations. Identification of tumor progression was further tested in SCID mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1. Significantly greater serum HA concentrations again corresponded with more rapid growth rates and invasiveness.


CONCLUSIONS
Serum HA concentrations predict the growth, invasion, and unfavorable histology findings of WT in a heterotransplant model. The authors further speculate that HA may foster an environment conducive to WT aggressiveness.
Division of Neonatology, The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, 19104, USA.
H N
HN
Lovvorn
R C
RC
Savani
E
E
Ruchelli
D L
DL
Cass
N S
NS
Adzick
D000818:Animals; D002648:Child; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D007680:Kidney Neoplasms / Q000097:blood* / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000473:pathology; D011379:Prognosis; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000097:blood* / Q000473:pathology*
D006820:Hyaluronic Acid