IDENTICAL GENETIC CHANGES IN DIFFERENT HISTOLOGIC COMPONENTS OF WILMS-TUMORS

Background: In young children and infants, Wilms' tumor is the most co mmon cancer of the kidney. Wilms' tumor exhibits heterogeneous histopa thologic features, consisting of rapidly proliferating blastemal and e pithelial cells and a stromal component that has heterologous elements (e.g,, cartilage, bone, and striated muscle), Ia. is unclear whether the stromal and heterologous components of sporadic Wilms' tumor are n eoplastic or should be considered non-neoplastic, Purpose: Our purpose was twofold: 1) to selectively analyze the different histologic tissu e components of sporadic Wilms' tumors, including blastemal, epithelia l, stromal, and heterologous elements, for loss of heterozygosity (LOH ) of the WT1 gene and for expression of the WT1 gene and 2) to determi ne the! role of WT1 gene expression in the development of these tissue s, Methods: By use of tissue microdissection techniques, various histo logic elements (blastema, stroma, epithelium, and striated muscle) of sporadic Wilms' tumor were obtained from specimens taken from 18 patie nts. DNA was extracted from the dissected tissue fragments, and DNA so lutions were amplified by use of the polymerase chain reaction and the polymorphic genomic markers D11S1392 and D11S904 to detect LOH at the WT1 gene locus (11p13). Three selected specimens with heterologous el ements and LOH af 11p13 were analyzed for expression of the WT1 gene h v means of the in situ reverse transcr iption-polymerase chain reactio n. Results: Nine (50%) of the 18 spesimens showed LOH at the WT1 locus . Although identical WTB. gene deletion was consistently observed in a ll of the various histologic components; of these nine specimens, WT1 gene expression was high in the blastemal and epithelial elements and low in the stromal and heterologous elements, Conclusions and Implicat ions: Identical allelic deletion at 11p13 in all components of the spo radic Wilms' tumors examined suggests that the stromal tissue componen ts are neoplastic rather than noneoplastic, In conjunction with variab le WT1 gene expression in the different histologic components, the res ults raise the possibility that undifferentiated blastemal cells are t he? precursors of the stromal and heterologous elements. Morphological ly benign stromal and heterologous elements may therefore be derived. from neoplastic cells. The developmental state of the various tissue c omponents of Wilms' tumor may he attributed to an altered residual WT1 gene that is required for the maturation of blastemal and epithelial cells hut flat is not required for the maturation of stromal and heter ologous elements.