ORIGINAL ARTICLE

Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma

M A Ghanem¹, G J van Steenbrugge², M K Sudaryo⁴, R B Mathoera², J M Nijman² and Th H van der Kwast³

¹ Urology Department, Menoufiya University, Menoufiya, Egypt
² Department of Paediatric Urology, Josephine Nefkens Institute, Erasmus MC, University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands
³ Department of Pathology, Josephine Nefkens Institute
⁴ The Netherlands Institute for Health Sciences, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands

Correspondence to:
Correspondence to:
Dr G J van Steenbrugge, Josephine Nefkens Institute, Room Be 430, Erasmus MC, University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands;
steenbrugge{at}path.azr.nl

Aims: To investigate the prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor Flt-1 in nephroblastoma and whether tumour microvessel density (MVD) immunoreactivity, determined by the CD31 antigen, is related to the expression of VEGF and Flt-1.

Methods: The expression of VEGF and Flt-1 and MVD were investigated by means of immunohistochemical analysis in 62 Wilms’s tumours. Patients were treated preoperatively with chemotherapy and had a mean follow up of 5.7 years.

Results: In general, VEGF and Flt-1 were expressed in normal kidney parenchyma and to a variable extent in the three main components of Wilms’s tumour, namely: the blastemal, epithelial, and stromal cells. In tumour tissue, 52% and 47% of blastemal cells were positive for VEGF and Flt-1, respectively. A non-significant correlation was found between the expression of VEGF and Flt-1 in blastemal and epithelial cells and the clinicopathological stage. MVD was significantly higher in VEGF and Flt-1 positive tumours than in VEGF and Flt-1 negative tumours. Univariate analysis showed that the expression of VEGF and Flt-1 in blastemal cells was indicative of clinical progression and tumour specific survival. In addition, MVD expression was indicative of clinical progression. Epithelial staining was of no prognostic value. In a multivariate analysis, VEGF protein expression by blastemal cells was an independent prognostic marker for clinical progression.

Conclusions: These results indicate that VEGF and Flt-1 protein expression are closely related to MVD and seem to be an important predictor for poor prognosis in treated patients with Wilms’s tumour. Therefore, the expression of these molecules in primary Wilms’s tumour may be useful in identifying those patients at high risk of tumour recurrence and in guiding antiangiogenic treatment.

Keywords: Wilms’s tumour; vascular endothelial growth factor; Flt-1; microvessel density; prognosis; immunohistochemistry

Abbreviations: BSA, bovine serum albumin; DAB, diaminobenzidine tetrahydrochloride dihydrate; MVD, microvessel density; PAP, peroxidase-antiperoxidase; PBS, phosphate buffered saline; VEGF, vascular endothelial growth factor

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