title: Vascular endothelial growth inhibitor (VEGI) is an independent indicator for invasion in human pituitary adenomas.
abstract: Pituitary ademonas are benign tumours from the pituitary gland but may have an invasive and destructive growth pattern. There is little understanding of the growth and progression control of pituitary tumours. In the present study, we investigated the expression of vascular endothelial growth inhibitor (VEGI), a vascular endothelial growth and apoptosis regulator and VEGI receptor Death Receptor-3 (DR3), in clinical pituitary tumours. Pituitary tumours from 95 patients were included in the study. Fresh pituitary tumours were obtained immediately after surgery and processed for histological and molecular-based analyses. Histopathological and clinical information including tumour size, tumour invasion and endocrine status were analyzed against the gene transcript expression of VEGI, DR3 and VEGF. VEGI and VEGF family and VEGF receptors were quantitatively determined for their gene transcript expression. The expression levels of VEGI were significantly lower in pituitary tumours which invaded the sella floor, and with suprasellar extension than in non-invasive tumours (p=0.0073). VEGI levels were also negatively correlated with cavernous sinus invasion stage (p<0.0001), in that a high level of VEGI was associated with low tumour grade. Multivariate analysis indicated that VEGI is an independent factor predictive of invasion (p=0.05). It was further demonstrated that the relationship between VEGI and pituitary tumour invasion were independent of the expression of VEGF and its receptors. Low levels of VEGI transcripts were associated with the intratumoural haemorrhage (p=0.05). Out of all the pituitary tumours, 59 were non-functional. Out of the functional tumours, it was found that follicle stimulating hormone (FSH)-expressing and gonadotrophic tumours tended to have markedly low levels of VEGI transcripts, compared with non-functional tumours (p=0.0026 and p=0.003, respectively). The opposite was seen with thyroid-stimulating hormone (TSH)-secreting tumours. Levels of DR3 in tumours with sella destruction were also lower than in those without destruction. VEGI, possibly via DR3, suppresses the aggressive nature of pituitary tumours and its expression level is closely linked to the invasion and destruction of the suprasellar and sella regions. It also has implications for the endocrine nature of these tumours. VEGI thus has an important predictive and prognostic value in patients with pituitary tumours.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing P. R. China. E-mail: jwttyy@sina.com or Professor Wen G. Jiang, Cardiff University-Capital Medical University Joint Centre for Biomedical Research, Cardiff University School of Medicine, Cardiff, U.K. jiangw@cf.ac.uk.
authors.forename: Wang
authors.initials: W
authors.lastname: Jia
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sander
authors.forename: Guijun
authors.initials: G
authors.lastname: Jia
authors.forename: Ming
authors.initials: M
authors.lastname: Ni
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Runchun
authors.initials: R
authors.lastname: Lu
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000236:Adenoma / Q000473:pathology*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000378:metabolism; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017931:DNA Primers; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D042461:Vascular Endothelial Growth Factor A
keywords: Pituitary adenoma; VEGI; death receptor-3; invasion