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
Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenomas. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method. Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin (STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by counting approximately 1000 nuclei of the tumor cells at ×400 magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting adenomas).
Subject(s)
Ki-67 Antigen/metabolism , Pituitary Neoplasms/metabolism , Prolactin/metabolism , Prolactinoma/metabolism , Adrenocorticotropic Hormone/metabolism , Adult , Cell Proliferation , Female , Follicle Stimulating Hormone/metabolism , Human Growth Hormone/metabolism , Humans , Immunohistochemistry , Luteinizing Hormone/metabolism , Male , Middle Aged , Thyrotropin/metabolism , Young AdultABSTRACT
A lot of data suggests endocrine gland-derived vascular endothelial growth factor (EG-VEGF) to be restricted to endocrine glands and to some endocrine-dependent organs. Many evidences show that EG-VEGF stimulates angiogenesis and cell proliferation, although it is not a member of the VEGF family. At the time, a lot of data regarding the role of this growth factor in normal development are available. However, controversial results have been published in the case of pathological conditions and particularly in malignant tumors. Thus, our present paper has been focused on the role of EG-VEGF in normal tissues and various malignant tumors and their angiogenic processes.
