The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer
The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer
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DOI：
10.1002/ijc.24852
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发表时间：
2010-03-15
影响因子：
6.4
通讯作者：
Nijman, Hans W.
中科院分区：
文献类型：
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作者：
Bijen, Claudia B. M.;Bantema-Loppe, Enja J.;Nijman, Hans W.
本研究的目的是调查经典的MHC I类和非经典的MHC（人类白细胞抗原-G [HLA-GJ]）表达在一个大型队列的子宫内膜癌患者，以确定这些细胞表面标志物的预后价值及其与临床病理变量的关系。使用以下单克隆抗体对包含554例患者的上皮性子宫内膜癌组织的组织微阵列进行经典和非经典MHC I类染色：084（抗HLA-G）、β 2-m（抗β 2-微球蛋白）和HC-10（MHC I类抗原重链）。表达数据与已知的临床病理学特征和生存率相关。在肿瘤细胞中分别观察到40%和48%的HLA-G上调和MHC I类下调。非胶质瘤样肿瘤类型、晚期疾病（FIGO分期>= II）和低分化或未分化肿瘤与MHC I类下调相关。HLA-G表达的缺失与MHC I类下调独立相关。在单因素分析中，MHC I类下调是较差的疾病特异性生存的预测因子。子宫内膜癌细胞中MHC I类分子表达下调与预后不良的肿瘤特征相关。此外，在大量子宫内膜癌患者队列中观察到，I类MHC下调对疾病特异性生存产生负面影响。由于经典和非经典MHC I类分子（HLA-G）之间似乎存在联系，因此有必要进一步研究以阐明这种调节机制。
The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-GJ) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological variables. Tissue microarrays containing epithelial endometrial carcinoma tissue from 554 patients were stained for classical and nonclassical MHC class I using the following monoclonal antibodies: 084 (anti-HLA-G), beta 2-m (anti-beta-2-microglobulin) and HC-10 (MHC class I antigen heavy chain). Expression data were linked to known clinicopathological characteristics and survival. HLA-G upregulation and MHC class I downregulation in neoplastic cells was observed in 40% and 48%, respectively. Nonendometrioid tumor type, advanced stage disease (FIGO stage >= II) and poorly or undifferentiated tumors were associated with MHC class I downregulation. Absence of HLA-G expression was independently associated with MHC class I downregulation. In univariate analysis, MHC class I downregulation was a predictor of worse disease-specific survival. Prognostic unfavorable tumor characteristics were correlated with downregulation of MHC class I expression in endometrial cancer cells. Furthermore, downregulated MHC class I has a negative impact on diseasespecific survival, observed in a large cohort of patients with endometrial cancer. As there seems to be a relation between classical and nonclassical MHC class I molecules (HLA-G), further research is warranted to unravel this regulatory mechanism.