Abstract
Angiogenesis (neoangiogenesis), a process of neovascularization, is an essential step for local tumor growth and distant metastasis formation. We have analysed angiogenesis status: vascular architecture, microvessel density, and vascular endothelial growth factors expression in 62 adrenal pheochromocytomas: 57 benign and 5 malignant. Immunohistochemical evaluation revealed that vascular architecture and vessel density are different in the central and subcapsular areas of the tumor. Furthermore, we have observed a strong correlation between number of macrophages and microvessel density in the central and subcapsular areas of the tumor and between the expression of VEGF-A in tumor cells and microvessel density in central and subcapsular areas of the tumor. Secondary changes in these tumors influence the results and both vascular architecture and microvessel density are markedly disturbed by hemorrhagic and cystic changes in pheochromocytomas. These changes are partially caused by laparoscopic operation technique. However, no differences in vascular parameters were found between pheochromocytomas with benign and malignant clinical behavior. Our observation showed that analysis of angiogenesis, as a single feature, does not help in differentiating malignant and benign pheochromocytomas and has no independent prognostic significance. On the other hand, high microvessel density in pheochromocytoma is a promising factor for antiangiogenic therapy in malignant cases.
Highlights
Adrenal pheochromocytoma (PCC) is an uncommon, neuroendocrine, catecholamine-secreting tumour arising from chromaffin cells of the adrenal medulla [1, 2]
The aim of the study was to compare Microvessel density (MVD), expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D), and the number of macrophages in different areas of 57 benign and 5 malignant tumors and to determine if angiogenesis evaluation can be useful in routine pathomorphological practice for predicting the clinical outcome of a particular PCC tumor
Most commonly used methods consist of assessing microvessel density (MVD) and expression of angiogenic factors, among which the most important are vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) [11, 12, 17]
Summary
Adrenal pheochromocytoma (PCC) is an uncommon, neuroendocrine, catecholamine-secreting tumour arising from chromaffin cells of the adrenal medulla [1, 2]. PASS criteria (Pheochromocytoma of the Adrenal Gland Scaled Score) were proposed in 2002 as a tool for differentiating between benign and malignant cases [9] but this scoring system is not perfect and has some limitations. Using this scale, a significant proportion of PCC receives boundary PASS values (PASS = 4 or 5) which do not allow for an unequivocal assignment of the tumor to a benign or International Journal of Endocrinology malignant group. It is necessary to find additional features that allow better prediction of the clinical malignant behavior of the tumor (future recurrence or metastasis).
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