de Figueiredo Feitosa Nathalie Lobo, Crispim Janaina Cristina de Oliveira, Zanetti Bruna Riedo, Magalhães Patrícia Kunzle Ribeiro, Soares Christiane Pienna, Soares Edson Garcia, Neder Luciano, Donadi Eduardo Antonio, Maciel Léa Maria Zanini
1 Division of Endocrinology & Metabolism, University of São Paulo , São Paulo, Brazil .
Thyroid. 2014 Mar;24(3):585-92. doi: 10.1089/thy.2013.0246. Epub 2014 Jan 20.
HLA-G is a nonclassical major histocompatibility complex molecule that has well-recognized immunomodulatory properties. The expression of HLA-G in tumor cells has been considered to be detrimental, permitting tumor spreading and decreased survival. We evaluated the expression of HLA-G in histologically normal thyroid tissue, goiter, and benign and malignant thyroid tumors, and studied the relationship between HLA-G expression and patient clinical variables.
The immunohistochemistry expression of HLA-G was performed on 72 specimens of papillary thyroid carcinoma (PTC), 19 follicular thyroid carcinomas (FTC), 22 follicular adenomas (FA), 22 colloid goiters (CG), and 14 histologically normal thyroid glands (NT). The percentage of HLA-G staining was graded from absent (-) to intense (+++).
HLA-G was faintly expressed in areas of hyperplasia in NT and CG. In PTC, FTC, and FA, the percentage of cell staining was significantly higher than in NT and CG (p<0.001 for each comparison). The tumor area with HLA-G expression was greater in FTC (p=0.0059) and PTC (p=0.0330) compared to FA. According to the magnitude of HLA-G staining, PTC tumors >1 cm exhibited increased HLA-G staining when compared to smaller tumors (p=0.03). Aggressive histologic subtypes of PTC have a higher median stained tumor area. No association was found between HLA-G expression and tumoral staging or patient disease-free survival.
The gradual increase of HLA-G expression from hyperplasia to carcinomas, and the association of strong HLA staining with some variables implicated in poor prognosis corroborate the unfavorable role of HLA-G in tumor thyroid cells, inhibiting cytotoxic immune system cells and facilitating tumor evasion and progression.
HLA - G是一种非经典的主要组织相容性复合体分子，具有公认的免疫调节特性。HLA - G在肿瘤细胞中的表达被认为是有害的，会促使肿瘤扩散并降低生存率。我们评估了HLA - G在组织学正常的甲状腺组织、甲状腺肿以及良性和恶性甲状腺肿瘤中的表达，并研究了HLA - G表达与患者临床变量之间的关系。
对72例乳头状甲状腺癌（PTC）、19例滤泡状甲状腺癌（FTC）、22例滤泡性腺瘤（FA）、22例胶样甲状腺肿（CG）和14例组织学正常的甲状腺（NT）标本进行HLA - G的免疫组化表达检测。HLA - G染色百分比从无（ - ）到强（ +++ ）进行分级。
HLA - G在NT和CG的增生区域微弱表达。在PTC、FTC和FA中，细胞染色百分比显著高于NT和CG（每次比较p<0.001）。与FA相比，FTC（p = 0.0059）和PTC（p = 0.0330）中具有HLA - G表达的肿瘤区域更大。根据HLA - G染色程度，与较小肿瘤相比，直径>1 cm的PTC肿瘤HLA - G染色增加（p = 0.03）。PTC侵袭性组织学亚型染色肿瘤面积中位数更高。未发现HLA - G表达与肿瘤分期或患者无病生存期之间存在关联。
从增生到癌HLA - G表达逐渐增加，以及强HLA染色与一些提示预后不良的变量之间存在关联，证实了HLA - G在甲状腺肿瘤细胞中的不利作用，即抑制细胞毒性免疫系统细胞并促进肿瘤逃逸和进展。
