Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted Wilms' tumor

Background/Purpose: The sera and urine of children with Wilms' tumor (WT) o ften contain increased concentrations of hyaluronan (HA). The authors devel oped a heterotransplant model to investigate whether serum HA concentration s could predict the histology and progression of WT. Methods: Random portions of 8 human WT specimens (7 favorable and 1 unfavor able histology findings) were heterotransplanted into the flanks of severe combined immunodeficient (SCID) mice. After 6 to 20 weeks of observation, a nimals 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 mu g/L (range, 459 to 3,206,176 mu g/L) compared with a median HA concentration of 416 mu g/L (range, 204 to 782 mu g/L) in animals not supp orting tumor growth. The highest serum HA concentrations were detected in a nimals harboring unfavorable histology blastemal-predominant tumors, wherea s animals supporting favorable histology epithelial- and stromal-predominan t tumors had the lowest serum HA concentrations. In association with marked ly increased serum HA, undifferentiated blastemal tumors showed significant ly greater growth rates than the more differentiated epithelial or stromal tumors. Additionally, serum HA concentrations were greater in mice with inv asive as compared with noninvasive tumors for each histological type. Compl ete 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 concentra tions again corresponded with more rapid growth rates and invasiveness. Conclusions: Serum HA concentrations predict the growth, invasion, and unfa vorable histology findings of WT in a heterotransplant model. The authors f urther speculate that HA may foster an environment conducive to WT aggressi veness. Copyright (C) 2000 by W.B. Saunders Company.