The Expression of Vascular Endothelial Growth Factor and Its Receptors in Congenital Bronchopulmonary Cystic Malformations

Background  Bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM) represent rare hamartomatous abnormalities of the lung. Dysregulation of cytokines that influence pulmonary vasculogenesis and epithelial growth, both known to be altered in BPS and CCAM, may play a role in their pathogenesis. Objective  We hypothesized that expression of vascular endothelial growth factor (VEGF) or its receptors might be altered in CCAM and BPS, possibly distinguishing CCAM from BPS, or from controls. Methods  Lung biopsy specimens obtained from infants who had undergone surgery for BPS ( n  = 4) or CCAM ( n  = 5) within the first month of life and normal lung autopsy samples ( n  = 4) serving as controls were investigated immunohistochemically for the protein expression levels of VEGF and its corresponding receptors. Results  VEGF, vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor receptor 3 (VEGFR3) staining was detected in CCAM and BPS specimens, as well as in control samples. VEGFR2 expression increased from controls to CCAM and from CCAM to BPS, the difference between controls and BPS being significant. The expression of VEGF, VEGFR1, and VEGFR3 was similar among the three groups. Consistent with a possible involvement of VEGFR2 in altered vasculogenesis-bronchiogenesis interaction, its expression was predominantly found in bronchial but not alveolar regions. Conclusions  The data suggest a possible role of VEGF-VEGFR2 interaction in the pathogenesis of congenital bronchopulmonary cystic malformations. However, VEGFR2 does not represent a suitable histochemical marker to distinguish between BPS and CCAM.