Vasconcelos Marcelo Gadelha, Vasconcelos Rodrigo Gadelha, Pereira de Oliveira Denise Hélen Imaculada, de Moura Santos Edilmar, Pinto Leão Pereira, da Silveira Éricka Janine Dantas, Queiroz Lélia Maria Guedes
Professor, State University of Paraíba, Campina Grande, Paraíba, Brazil.
PhD Student, Postgraduate Program, Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
J Oral Maxillofac Surg. 2015 Sep;73(9):1753-60. doi: 10.1016/j.joms.2015.03.013. Epub 2015 Mar 18.
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-1α (HIF-1α) 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).
The sample included 57 cases of TSCC. Histologic sections of 3 μm were submitted to the immunoperoxidase method and semiquantitative analysis. The association between HIF-1α and GLUT-1 expression in TSCC and the clinical stage and the HGS of Bryne (1998) was evaluated using the χ(2) test, with the significance level set at 0.05 (α = 0.05).
HIF-1α 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-1α expression correlated significantly with clinical stage (P = .011) and HGS (P = .002). A significant association was observed between the distribution of HIF-1α 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).
The expression of HIF and GLUT proteins within TSCC appears to be associated with disease stage, grade, and the presence of metastases. Additional studies are needed to evaluate the diagnostic and prognostic uses of these proteins in the treatment of TSCC.
口腔鳞状细胞癌具有快速且不受限生长的潜能。因此，缺氧组织区域在这些恶性肿瘤中很常见，并促进癌症进展、治疗抵抗及不良预后。本研究的目的是分析舌鳞状细胞癌（TSCC）病例中缺氧诱导因子-1α（HIF-1α）和葡萄糖转运蛋白-1（GLUT-1）的基因产物分布，并确定这些蛋白与临床分期及布赖恩斯组织学分级系统（HGS）之间的初步相关性。
样本包括57例TSCC。将3μm的组织切片进行免疫过氧化物酶法及半定量分析。使用χ²检验评估TSCC中HIF-1α和GLUT-1表达与临床分期及布赖恩斯（1998年）HGS之间的关联，显著性水平设定为0.05（α = 0.05）。
HIF-1α主要表达于肿瘤细胞的细胞核/细胞质中，大多数标本在肿瘤细胞中呈现弥漫性染色（84.2%），仅在坏死周边区域观察到局灶性染色（15.8%）。GLUT-1表达于恶性细胞的细胞质和细胞膜中，所有病例均观察到弥漫性染色。HIF-1α表达强度与临床分期（P = 0.011）和HGS（P = 0.002）显著相关。观察到HIF-1α表达分布与转移之间存在显著关联（P = 0.040）。GLUT-1的免疫表达与临床分期（P = 0.002）和HGS（P = 0.000）显著相关。在大多数低级别肿瘤中，外周岛状区域的GLUT-1表达占主导（78.6%）；在高级别病例中，表达在肿瘤岛的中心/周边区域占优势（55.8%）。不同组织学分级中肿瘤岛位置的比较显示出统计学显著差异（P = 0.025）。
TSCC中HIF和GLUT蛋白的表达似乎与疾病分期、分级及转移的存在相关。需要进一步研究以评估这些蛋白在TSCC治疗中的诊断和预后用途。
