Extrarenal Wilms' tumors. A study of their relationship with classical renal Wilms' tumor using expression of WT1 as a molecular marker.
BACKGROUND: Wilms' tumors (WT) are renal malignancies typically of childhood with classic histopathologic features. A candidate WT gene (WT1) has been described, expression of which is largely restricted to the developing genitourinary system. WT1 is highly expressed in most sporadic childhood renal WT, and inactivating mutations have been described, consistent with its role as a tumor suppressor gene. WT1, therefore, may be used as a molecular marker for renal WT in most cases. Rarely, do tumors, that histologically resemble WT, develop in adult kidneys or exceptionally at nonrenal sites. This study addresses the question, are extrarenal tumors that have the morphology of renal WT really a type of WT? We investigated this question by using WT1 expression as a molecular marker for WT. EXPERIMENTAL DESIGN: We studied WT1 expression in eight well-documented cases of extra-renal WT by RNA-RNA in situ hybridization using an 35S-labeled probe derived from a cloned WT1 gene sequence. RESULTS: WT1 mRNA expression was detected in 5 of 5 childhood cases of sporadic childhood renal WT and 2 of 8 extrarenal WT. Both WT1-positive extrarenal WT were endometrial primaries. The WT1-negative extrarenal WT included retroperitoneal (3), pararenal or paravesical (2), and paraspinal (1) primaries. The seven non-WT uterine malignancies (carcinomas and sarcomas) studied were WT1-negative. CONCLUSIONS: These findings suggest that some cases of extrarenal WT are related to classical renal WT by more than mere morphologic resemblance, as indicated by the detection of WT1 mRNA expression in at least a subset of these rare tumors. Furthermore, the results suggest different pathogeneses of subsets of extrarenal WT.