TTF-1 Expression in Nephroblastoma

ArticleinThe American journal of surgical pathology 33(3):454-61 · December 2008with11 Reads
DOI: 10.1097/PAS.0b013e318185d21b · Source: PubMed
The unexpected observation of nuclear immunoreactivity for thyroid transcription factor-1 (TTF-1) associated with an apparent lack of nuclear immunoreactivity for Wilms tumor-1 protein (WT1) in the pulmonary metastasis of a morphologically typical case of nephroblastoma affecting a 6.5-year-old male prompted us to examine the expression of these 2 markers (and CD56) in a series of 48 nephroblastomas, 5 adult metanephric adenomas, and 1 pediatric cystic nephroma. TTF-1 was found to be positive in 8 of 48 (16.6%) nephroblastomas and negative in all 5 metanephric adenomas. WT1 was positive in 43 of 48 (89.6%) nephroblastomas and 4 of 5 (80.0%) metanephric adenomas. CD56 was positive in 45 of 47 cases that were so tested (95.74%), but negative in all metanephric adenomas. The single cystic nephroma was TTF-1-negative, WT1-negative, and CD56-positive. The finding of TTF-1 expression in one sixth of nephroblastomas constitutes a potential source of misdiagnosis. The biologic significance of this surprising finding is unclear. It may reflect the embryonal nature of these tumors and may conceivably result-directly or indirectly-in interference with the transcriptional control of target genes and other molecular events in the pathway leading to the development of nephroblastoma.
    • "These fi ndings may also explain the expression of WT1 in many human mesothelial-derived tumors, such as mesothelioma (K umar-S ingh et al., 19 9 7; N ak atsuk a et al., 2006), ovarian tumors (S himiz u et al., 2000; Z hang et al., 2003 ; Z hao et al., 2007) and S ertoli cell tumors (Z hao et al., 2007). S ome authors have previously reported a strong cytoplasmic staining in human rhabdomyosarcoma (C arpentieri et al., 2002; Bisceglia et al., 2011), a tumor composed of malignant mesenchymal cells show ing morphological, immunohistochemical and ultrastructural features of sk eletal muscle differentiation, and in rhabdomyomatous Wilms' tumor (Bisceglia et al., 2009 ). The authors excluded the possibility of WT1 expression in developing sk eletal muscle of an 8 -w eek s' gestation fetus. "
    [Show abstract] [Hide abstract] ABSTRACT: The Wilms' tumor (WT1) gene and its protein product are known to exhibit a dynamic expression profile during development and in the adult organism. Apart from a nuclear expression observed in the urogenital system, its precise localization in other developing human tissues is still largely unknown. Accordingly, the aim of this study was to investigate immunohistochemically the temporal and spatial distribution of WT1 in epithelial and mesenchymal developing human tissues from gestational weeks 7-24. For this purpose we used antibodies against the N-terminal of WT1. As might be expected, WT1 nuclear expression was observed in mesonephric/metanephric glomeruli, metanephric blastema, celom-derived membranes (pleura, peritoneum, serosal surfaces) and sex cords. With regard to mesenchymal tissues, a similar nuclear staining was also obtained in the mesenchyme surrounding Müllerian and Wolffian ducts, as well as in the submesothelial mesenchymal cells of all celomatic-derived membranes. The most striking finding was the detection of strong WT1 cytoplasmic immunostaining in developing skeletal and cardiac muscle cells and endothelial cells. The tissue-specific expression of WT1, together with its different nuclear/cytoplasmic localization, both suggest that WT1 protein may have shuttling properties, acting as a protein with complex regulator activity in transcriptional/translation processes during human ontogenesis. The reported cytoplasmic expression of WT1 in human rhabdomyosarcomas and in many vascular tumors strongly suggests an oncofetal expression of this protein. Although not specific, WT1 cytoplasmic expression can be used as a marker of skeletal muscle and endothelial differentiation in an appropriate morphological context.
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