title: Expression of vascular endothelial growth factor (VEGF) and its receptors (VEGF-R1 [Flt-1] and VEGF-R2 [KDR/Flk-1]) in tumorlets and in neuroendocrine cell hyperplasia of the lung.
abstract: Pulmonary tumorlets and neuroendocrine (NE) cell hyperplasia are part of a continuous spectrum of NE-cell hyperplasia, going from NE hyperplasia to carcinoid. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that has been shown to be increased in hypoxic lung. We hypothesized that tumorlets and NE-cell hyperplasia, which occur frequently in this context, were partly responsible for VEGF secretion. Immunohistochemical analysis of VEGF and both VEGF-R1 and VEGF-R2 was performed on paraffin sections of 12 lung tissues containing tumorlets and NE-cell hyperplasia in parallel with a control group of 11 lung specimens. VEGF and its receptor expressions were compared in bronchial epithelial cells and endothelial cells in both groups. VEGF and its receptors were consistently expressed in tumorlets and in NE-cell hyperplasia. When compared with control group lungs, the staining score for VEGF in lung bearing tumorlets was significantly higher in endothelial cells, but was not different in bronchial epithelial cells. VEGF-R1 expression was significantly increased both on bronchial epithelial cells (P = 0.001) and endothelial cells (P = 0.006), and VEGF-R2 expression was significantly increased on endothelial cell (P = 0.044). There was a significant positive correlation between the level of expression of VEGF and VEGF-R1 (P = 0.04) in both control groups and lung bearing tumorlets, but there was no significant correlation between VEGF and VEGF-R2 expression (P = 0.1). We concluded that VEGF is highly expressed in localized NE cell proliferations without potential of malignancy and might participate in local development of fibrosis.
authors.affiliation: Laboratoire de Pathologie Cellulaire, Département de Médecine Aiguë Spécialisée, Service de Chirurgie Thoracique, and Lung Cancer Research Group (INSERM U 578), CHU Albert Michallon, Grenoble, Franc.
authors.forename: Hervé
authors.initials: H
authors.lastname: Sartelet
authors.forename: Myriam
authors.initials: M
authors.lastname: Decaussin
authors.forename: Gilles
authors.initials: G
authors.lastname: Devouassoux
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nawrocki-Raby
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Brichon
authors.forename: Christian
authors.initials: C
authors.lastname: Brambilla
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brambilla
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2