ABSTRACT
Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.
Subject(s)
Adenoma/metabolism , Pituitary Hormones/analysis , Pituitary Neoplasms/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor, Endocrine-Gland-Derived/metabolism , Adenoma/genetics , Adenoma/pathology , Adenoma, Acidophil/genetics , Adenoma, Acidophil/metabolism , Adenoma, Acidophil/pathology , Adenoma, Basophil/genetics , Adenoma, Basophil/metabolism , Adenoma, Basophil/pathology , Adenoma, Chromophobe/genetics , Adenoma, Chromophobe/metabolism , Adenoma, Chromophobe/pathology , Gene Expression Regulation , Humans , Immunohistochemistry , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor, Endocrine-Gland-Derived/geneticsABSTRACT
In the pituitary gland, activating mutations of the GNAS1 (Gsalpha) gene at Gln227 have been identified in adrenocorticotrophin secreting, growth hormone secreting, and prolactin secreting adenomas. To date, mutations at the codon encoding R201, typically underlying the McCune-Albright syndrome and isolated fibrous dysplasia of bone, have been demonstrated only in growth hormone secreting pituitary adenomas. In this study, a polymerase chain reaction amplified target sequence in exon 8 of the GNAS1 gene was sequenced, identifying the first R201 mutation seen in an isolated basophilic adenoma which generated Cushing's disease in a child. This case adds Cushing's disease to the range of human diseases caused by R201 mutations of the GNAS1 gene.
