EXPRESSION OF THE RNA COMPONENT OF TELOMERASE IN WILMS-TUMOR AND NEPHROGENIC REST RECAPITULATES RENAL EMBRYOGENESIS

Telomerase is a ribonucleoproteiu enzyme associated with cellular immo rtality and has been detected in the vast majority of adult tumors. Wi lms tumor is a histologically diverse embryonal malignancy of childhoo d, and the histological features of Wilms tumor and its precursor lesi on, the nephrogenic rest, recapitulate the components of normal renal embryogenesis. Both the epithelial and the stromal components of Wilms tumor arise by differentiation of primitive mesodermal blastema. We c ompared expression of the RNA component of human telomerase (hTR) in n ormal developing kidneys, Wilms tumors, and nephrogenic rests and corr elated expression of hTR with cell proliferation. Using a radioactive in situ hybridization method, we examined archival material from 17 Wi lms tumors (including nine with nephrogenic rests), four therapeutical ly aborted embryos (37 to 56 days), three fetuses on whom autopsies ha d been performed, and one neonate for expression of hTR. Proliferative index was measured by Immunohistochemical staining for MIB1. In the e mbryonic kidney, Wilms tumors, and nephrogenic rests, the patterns of hTR expression were similar: expression was usually maximal within the immature epithelial elements followed by the poorly differentiated bl astema, but was weak or absent in the immature stroma. Mature tubules, glomeruli, and stroma were negative for hTR expression, as were diffe rentiated heterologous elements present in post-therapy Wilms tumors. There was only a partial relationship between proliferative index and hTR expression. In the embryonic kidney, Wilms tumors, and nephrogenic rests, blastema had the highest proliferative index, whereas the indi ces were significantly lower in the immature epithelium and stroma. Th e proliferative index in mature and heterologous elements was low or z ero. Thus, the pattern of hTR expression In Wilms tumor and its precur sor lesion recapitulates embryogenesis precisely and may represent tha t aspect of the persistent fetal phenotype which predisposes to the de velopment of malignancy. Copyright (C) 1998 by W.B. Saunders Company.