Hypoxia-inducible factor-1α (HIF-1α) promotes proteins that enable cell survival during hypoxia, such as glucose transporter 1 (GLUT-1). Their coexpression has been associated with aggressiveness in malignancies and has not been studied in odontogenic tumors. Immunohistochemical expression of HIF-1α and GLUT-1 was analyzed in 13 tooth germs (TGs), 55 ameloblastomas (AMs), and 3 ameloblastic carcinomas (ACs). HIF-1α was negative in all TGs, and just 1 case of AM and 1 of AC had nuclear positivity. GLUT-1 expressed in ameloblastic cells of all TGs, AMs, and ACs, with an increasing intensity, respectively, and was significantly higher in solid AM than in unicystic AM (P = .041). Absence of nuclear HIF-1α in TGs and most AMs suggest that GLUT-1 may be induced by alternative pathways to hypoxia. However, in ACs, HIF-1α may be activated; however, to confirm this, additional cases are needed. GLUT-1 overexpression could be related to aggressiveness in AMs and ACs and must represent a normal metabolite in TGs.
BarnesLEvesonJWReihcartPSidranskyD, eds. WHO International Histological Classification of Tumours. Vol 9. Lyon, France: IARC Press; 2005:285-300.
2.
SeintouAMartinelli-KläyCPLombardiT. Unicystic ameloblastoma in children: systematic review of clinicopathological features and treatment outcomes. Int J Oral Maxillofac Surg. 2014;43:405-412.
3.
Martínez MartínezMMosqueda-TaylorACarlosRDelgado-AzañeroWde AlmeidaOP. Malignant odontogenic tumors: a multicentric Latin American study of 25 cases. Oral Dis. 2014;20:380-385.
4.
CostaAFTassoMGMarianoFVLevels and patterns of expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation. Histopathology. 2012;60:816-825.
5.
ReisserCEichhornKHerold-MendeCBornAIBannaschP. Expression of facilitative glucose transport proteins during development of squamous cell carcinomas of the head and neck. Int J Cancer. 1999;80:194-198.
6.
CarvalhoKCCunhaIWRochaRMGLUT1 expression in malignant tumors and its use as an immunodiagnostic marker. Clinics (Sao Paulo). 2011;66:965-972.
7.
EckertAWLautnerMHTaubertHSchubertJBilkenrothU. Expression of Glut-1 is a prognostic marker for oral squamous cell carcinoma patients. Oncol Rep. 2008;20:1381-1385.
8.
YasudaMMiyazawaMFujitaMExpression of hypoxia inducible factor-1alpha (HIF-1alpha) and glucose transporter-1 (GLUT-1) in ovarian adenocarcinomas: difference in hypoxic status depending on histological character. Oncol Rep. 2008;19:111-116.
9.
de OliveiraDHda SilveiraEJde MedeirosAMAlvesPMQueirozLM. Study of the etiopathogenesis and differential diagnosis of oral vascular lesions by immunoexpression of GLUT-1 and HIF-1α. J Oral Pathol Med. 2014;43:76-80.
10.
ChangKPKaoHKLiangYOverexpression of activin A in oral squamous cell carcinoma: association with poor prognosis and tumor progression. Ann Surg Oncol. 2010;17:1945-1956.
11.
BursteinDENagiCKohtzDSLeeLWangB. Immunodetection of GLUT1, p63 and phospho-histone H1 in invasive head and neck squamous carcinoma: correlation of immunohistochemical staining patterns with keratinization. Histopathology. 2006;48:717-722.
12.
AbdouAGEldienMMElsakkaD. GLUT-1 expression in cutaneous basal and squamous cell carcinomas. Int J Surg Pathol. 2015;23:447-453.
13.
AngadiVCAngadiPV. GLUT-1 immunoexpression in oral epithelial dysplasia, oral squamous cell carcinoma, and verrucous carcinoma. J Oral Sci. 2015;57:115-122.
14.
PiñaARMartínezMMde AlmeidaOP. Glut-1, best immunohistochemical marker for perineurial cells. Head Neck Pathol. 2015;9:104-106.
15.
AirleyRLoncasterJDavidsonSGlucose transporter GLUT 1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. Clin Cancer Res. 2001;7:928-934.
16.
SemaanAMunkarahARArabiHExpression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction. Gynecol Oncol. 2011;121:181-186.
17.
TakanagaHFrommerWB. Facilitative plasma membrane transporters function during ER transit. FASEB J. 2010;24:2849-2858.
AyalaFRRochaRMCarvalhoKCGLUT1 and GLUT3 as potential prognostic markers for oral squamous cell carcinoma. Molecules. 2010;15:2374-2387.
20.
RumayorACarlosRKirschHMde AndradeBARomañachMJde AlmeidaOP. Ghost cells in pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor: histological, immunohistochemical, and ultrastructural study. J Oral Pathol Med. 2015;44:284-290.
21.
MohamedKMLeADuongHWuYZhangQMessadiDV. Correlation between VEGF and HIF-1alpha expression in human oral squamous cell carcinoma. Exp Mol Pathol. 2004;76:143-152.
LiangXYangDHuJHaoXGaoJMaoZ. Hypoxia inducible factor-alpha expression correlates with vascular endothelial growth factor-C expression and lymphangiogenesis/angiogenesis in oral squamous cell carcinoma. Anticancer Res. 2008;28:1659-1666.
24.
RyanHELoJJohnsonRS. HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 1998;17:3005-3015.
25.
SainiYHarkemaJRLaPresJJ. HIF1 alpha is essential for normal intrauterine differentiation of alveolar epithelium and surfactant production in the newborn lung of mice. J Biol Chem. 2008;283:33650-33657.
