Expression of Notch Pathway Components in Wilms' Tumour.
Raffaella Santi, Milena Paglierani, Monica Pepi, Daniela Massi, Gabriella Nesi. University of Florence, Italy
Background: Wilms' tumour (nephroblastoma) is the most common kidney cancer in childhood. It derives from embryonic renal precursors and is often associated with lasting embryonic renal tissue. Notch signalling plays a crucial role in many developmental processes and may contribute to oncogenesis in a tissue-specific manner. Recent studies document the expression of Notch pathway proteins during nephrogenesis. The aim of this study was to investigate the expression and patterning of Notch pathway components in a series of Wilms' tumours.
Design: Fourteen primary nephroblastomas and five nephroblastoma metastases to the lung were reviewed on haematoxylin-eosin stained slides. Notch-1 and Notch-2 protein expression was studied by immunohistochemical assay. Tissue sections were labelled with the following antibodies: goat anti-human Notch-1 (sc-6014) and goat anti-human Notch-2 (sc-5545) (Santa Cruz Biotechnology Inc.).
Results: There were 10 females and 6 males, ranging from six months to 34 years of age. On light microscopy, the surgical specimens harboured triphasic (n=7; 36%), biphasic (n=6; 32%) or monophasic (n=6; 32%) lesions. Among the 14 cases displaying an epithelial component, Notch-2 immunostaining was detected in 10 (71%), whereas only in 3/17 (18%) cases blastema showed faint and focal Notch-2 reactivity. The stromal component showed variable degrees of Notch-2 immunoreactivity with a higher intensity in tumours exhibiting myogenic features. In all cases, normal renal tissue and vascular endothelial cells were strongly and diffusely positive for Notch-2. Notch-1 expression substantially overlapped Notch-2 immunohistochemical results, although with a lower intensity of staining.
Conclusions: Preliminary results of this study indicate a decreased expression of Notch-2 and Notch-1 proteins in the blastema, when compared with the epithelial and the myogenic components or the peritumoral renal parenchyma. Further studies are needed to better assess the role of Notch signalling in nephroblastoma oncogenesis and its putative interactions with pathways involved in tumour progression and invasiveness.
Monday, February 28, 2011 1:00 PM
Poster Session II # 199, Monday Afternoon