Distribution of Hypoxia-Inducible Factor-1α and Glucose Transporter-1 in Human Tongue Cancers

Abstract

Purpose: Oral squamous cell carcinomas have the potential for rapid and unlimited growth. Therefore, hypoxic tissue areas are common in these malignant tumors and contribute to cancer progression, therapy resistance, and poor outcomes. The aim of the present study was to analyze the gene product distribution of hypoxia-inducible factor-1a (HIF-1a) and glucose transporter-1 (GLUT-1) in cases of tongue squamous cell carcinoma (TSCC) and to identify a preliminary correlation between these proteins and clinical staging and Brynes's histologic grading system (HGS). Materials and Methods:The sample included 57 cases of TSCC. Histologic sections of 3 mm were submitted to the immunoperoxidase method and semiquantitative analysis. The association between HIF-1a and GLUT-1 expression in TSCC and the clinical stage and the HGS of Bryne (1998) was evaluated using the c 2 test, with the significance level set at 0.05 (a = 0.05).Results: HIF-1a was mainly expressed in the nucleus/cytoplasm of neoplastic cells, most specimens exhibited diffuse staining in neoplastic cells (84.2%), and focal staining was only observed in perinecrotic areas (15.8%). GLUT-1 was expressed in the cytoplasm and membrane of malignant cells, and diffuse staining was observed in all cases. The intensity of HIF-1a expression correlated significantly with clinical stage (P = .011) and HGS (P = .002). A significant association was observed between the distribution of HIF-1a expression and metastasis (P = .040). Immunoexpression of GLUT-1 correlated significantly with clinical stage (P = .002) and HGS (P = .000). GLUT-1 expression in the peripheral island was predominant in most low-grade tumors (78.6%); in the high-grade cases, the expression prevailed in the location center/periphery (55.8%). Comparison of the location of the tumor island in the different histologic grades showed a statistically significant difference (P = .025).

Prognostic value of GLUT-1 expression in oral squamous cell carcinoma

“…HIFs and GLUT-1 were found to be both overexpressed in OSCC. [25] The relevance between HIFs and GLUT-1 could support the important role of energy supply for tumor cells. In the present meta-analysis, we included studies detecting GLUT-1 by unified method, IHC, to reduce heterogeneity.…”

Clinical and prognostic significance of HIF-1α overexpression in oral squamous cell carcinoma: a meta-analysis

“…3), which suggested an association between HIF-1α expression and tumor size. In six studies [6, 19–21, 25, 26], patients with stage III/IV OSCC had higher levels of HIF-1α expression as compared to that in patients with stage I/II tumors. The combined OR was significant (OR = 2.29, 95% CI = 1.50–3.49, I 2  = 37.3%, P  = 0.158; fixed-effects model) with no significant heterogeneity (Fig.…”

Hypoxia in oral squamous cell carcinoma: A breath of fresh air in cancer research?

“…[8] Among the hypoxic markers, HIF-1α has been studied commonly either alone or mainly with other markers like HIF-2α, [10,12,13] CA-IX, [10,14,15] GLUT-1, [10,14,16,17] and VEGF. [10,[13][14][15][18][19][20][21] Increased HIF-1α expression has been found to be significantly correlated with clinicopathological variables such as clinical stage, histopathological grade, and lymph node involvement in many studies, [12,14,16,18] with correlation with only clinical stage and lymph node involvement in some, [22][23][24] with tumor size [23,24] and in some even with recurrences. [15,17] The expression of HIF-1α was localized to the nucleus and was distributed heterogeneously throughout the tumor area especially in the perinecrotic regions, and at the tumor/stroma interface.…”

“…GLUT-1 upregulation in response to hypoxia has been found in multiple cell and tissue types. [14,16,17,27] In patients where the tumor had increased levels of both HIF-1α and GLUT-1, there was a 5.13 fold increased risk of tumor-related deaths. [17] HIF and GLUT proteins within tongue squamous cell carcinoma (TSCC) appear to be associated with disease stage, grade, and the presence of metastases.…”

“…[17] HIF and GLUT proteins within tongue squamous cell carcinoma (TSCC) appear to be associated with disease stage, grade, and the presence of metastases. [16] Pedersen et al suggested that GLUT-1 expression is a constitutive characteristic of the malignant phenotype and is induced by RAS and SRC oncogenes. [30] Cross talk between VEGF and GLUT-1…”