Expression and localization of HGF and met in Wilms' tumours

A number of growth factors and cognate receptors that contribute to normal kidney development have been shown to play roles in the pathogenesis of Wilms' tumours. Expression of both hepatocyte growth factor (HGF) and its tyrosine kinase receptor met has been demonstrated in normal tissues and their neoplastic counterparts, implicating these factors in normal development and tumour progression. HGF and met expression has not been studied in Wilms' tumour. Since HGF and met function in a paracrine fashion by regulating tubulogenesis in normal kidney development, they could be involved in the pathogenesis of Wilms' tumour, in which tubular formation is dysplastic. In the present study, a series of ten homotypic (consisting of blastemal, epithelial, and stromal elements) and ten heterotypic (consisting of triphasic histology and a muscle component) Wilms' tumour cases were examined for expression of HGF and met, using in situ hybridization, immunohistochemistry, and western blot analysis. Relatively high met message and protein expression, compared with normal kidney, were evident in homotypic and heterotypic tumour blastemal, epithelial, and rhabdomyoblastic cells and a 145 kD met polypeptide was found in all tumours, with a few cases also expressing the 170 kD precursor form. No apparent alterations of the met receptor were observed. Similarly, HGF protein was also abundantly expressed in blastemal, epithelial, and rhabdomyoblastic cells of the homotypic and heterotypic Wilms' tumours and a 69 kD HGF polypeptide was demonstrated by western blot analysis. Immunohistochemistry for the Ki-67 proliferation marker indicated that the pattern of Ki-67 expression correlated with the HGF and met pattern of expression in both homotypic and heterotypic tumours. These results reveal, for the first time, significant co-expression of met/HGF in Wilms' tumours, with a correspondingly high proliferative index in the same cell groups.