Abstract
Ameloblastomas are epithelial odontogenic tumours that, although benign, are locally invasive and may exhibit aggressive behaviour. In the tumour microenvironment, the concentration of oxygen is reduced, which leads to intratumoral hypoxia. Under hypoxia, the crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. This work showcases 24 ameloblastoma cases, 10 calcifying odontogenic cysts, and 9 dental follicles, used to investigate the expression of these proteins by immunohistochemistry. The anti-HIF-1α, anti-MMP-2, anti-VEGF, and anti-VEGFR-2 primary antibodies are used in this work. The results have been expressed by the mean grey value after immunostaining in images acquired with an objective of 40×. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour.
Highlights
Ameloblastomas are epithelial odontogenic tumours that, benign, are locally invasive and may exhibit aggressive behaviour
VEGF receptors (VEGFRs)-2 showed immunostaining in the cell membrane of tumour cells (Fig. 4A,B)
HIF-1α binds with the HIF-1β subunit, becoming active and migrating to the cell nucleus in order to regulate cell survival m echanisms[35], this corroborates with our findings, suggesting that the HIF-1α found was active
Summary
Ameloblastomas are epithelial odontogenic tumours that, benign, are locally invasive and may exhibit aggressive behaviour. The crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour. The concentration of oxygen in the microenvironment around the tumour cells is reduced, resulting in intratumoral hypoxia, characterized by reduced oxygen pressure in the cells, which leads to various biochemical responses and may result in a number of compensatory cellular mechanisms that allow the continuation of neoplastic development. Hypoxia is associated with a more aggressive phenotype, which affects angiogenesis and cellular invasiveness[4,5]
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