Expression of the RNA component of telomerase in wilms tumor and nephrogenic rest recapitulates renal embryogenesis

Telomerase is a ribonucleoprotein enzyme associated with cellular immortality and has been detected in the vast majority of adult tumors. Wilms tumor is a histologically diverse embryonal malignancy of childhood, and the histological features of Wilms tumor and its precursor lesion, 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 compared expression of the RNA component of human telomerase (hTR) in normal developing kidneys, Wilms tumors, and nephrogenic rests and correlated expression of hTR with cell proliferation. Using a radioactive in situ hybridization method, we examined archival material from 17 Wilms tumors (including nine with nephrogenic rests), four therapeutically aborted embryos (37 to 56 days), three fetuses on whom autopsies had been performed, and one neonate for expression of hTR. Proliferative index was measured by immunohistochemical staining for MIB1. In the embryonic 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 blastema, but was weak or absent in the immature stroma. Mature tubules, glomeruli, and stroma were negative for hTR expression, as were differentiated 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 indices were significantly lower in the immature epithelium and stroma. The proliferative index in mature and heterologous elements was low or zero. Thus, the pattern of hTR expression in Wilms tumor and its precursor lesion recapitulates embryogenesis precisely and may represent that aspect of the persistent fetal phenotype which predisposes to the development of malignancy.