Correlations of Vascular Architecture and Angiogenesis with Pituitary Adenoma Histotype

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in solid tumors. However, its role in angiogenesis in pituitary adenoma is controversial. Angiogenesis in solid tumors including pituitary adenoma is commonly evaluated by microvascular density (MVD). Here, we evaluated MVD and the role of VEGF in vascular architecture in 51 pituitary adenomas (24 nonfunctioning, 13 prolactin-secreting, 10 growth hormone-secreting, 3 adrenocorticotropic hormone-secreting, and 1 thyroid-stimulating hormone-secreting). Paraffin sections were stained with CD34 and VEGF. MVD and vascular architecture parameters (vessel area, diameter, perimeter, and roundness) were evaluated in CD34-stained sections. Immunohistochemistry showed 27/51 tumors (53%) were VEGF-positive. There were no significant differences in MVD, any vascular parameter, or adenoma volume between VEGF-positive and VEGF-negative tumors. VEGF mRNA expression was significantly higher in VEGF-positive tumors. There were no significant correlations between VEGF mRNA expression and MVD or vascular parameters. However, vessel diameter and perimeter were significantly larger in prolactin-secreting than nonfunctioning and growth hormone-secreting macroadenomas. The difference in vessel diameter was observed among both VEGF-positive and all adenomas (micro- and macroadenoma). Thus, VEGF may have limited roles in the development of vascular architecture and tumor angiogenesis in pituitary adenomas, but the differences in vessel architecture by histotype (i.e., larger vessel diameter and perimeter in prolactin-secreting adenomas) suggest the hormonal regulation of vessel architecture rather than angiogenesis

Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution

“…In this context, the spatial relationship between the capillaries and the endocrine cells plays an important role regulating their secretory function. Previous reports have shown that microvascular density of pituitary tumours is smaller than in normal pituitary gland, and the density varies with adenoma histotypes234.…”

The role of the tumour microenvironment in the angiogenesis of pituitary tumours

“…Some previous studies have investigated angiogenesis in PitNETs [11][12][13][17][18][19][20][21][22][23]. However, research specifically studying the role of the different elements of the TME in the modulation of PitNET neovascularisation is scarce [24], contrasting with the extensive data available for other cancers [25][26][27].…”

Immunochistochemical characteristics of blood vessels in non-visualized and visualized on MRI pituitary adenoma in patients with Cushing’s disease

“…Объем удаленной в ходе операции опухоли в этих случаях, как правило, сопоставим с объемом визуализирующихся аденом гипофиза, однако возникают объективные сложности с получением материала для гистологического исследования, связанные с потерей ткани в ходе нейрохирургических манипуляций. Мы не нашли в литературе данных для сравнения с нашими результатами, поскольку исследования строения и свойств сосудов ранее проводилась в основном в макроаденомах гипофиза (в нашем исследовании лишь 27% опухолей приходилось на макроаденомы) [12,13]. К тому же, в таких исследованиях применялась разная методика оценки свойств сосудов, отличались и единицы площади исследуемых областей, что прежде всего связано с разным оптическим разрешением микроскопов и программным обеспечением.…”

“…Широко используемым методом оценки строения и свойств сосудов в опухолях человека является подсчет микрососудов с помощью специфических маркеров эндотелиальных клеток, таких как CD31 и CD34. Выбор иммуногистохимического маркера для оценки строения и свойств сосудов аденом основан на опыте ранее проведенных работ [12][13][14].…”