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口腔黏膜表皮样癌中程序性细胞死亡配体 1、人类白细胞抗原 G 和 E 以及颗粒酶 B 的免疫组织化学研究。

Immunohistochemical investigations on the expression of programmed cell death ligand 1, human leukocyte antigens G and E, and granzyme B in intraoral mucoepidermoid carcinoma.

机构信息

Federal University of Goiás, Faculty of Dentistry, Department of Stomatology (Oral Pathology), Goiânia, Brazil.

Araújo Jorge Hospital, Association of Cancer Combat of Goiás, Division of Anatomopathology and Cytopathology, Goiânia, Brazil.

出版信息

Arch Oral Biol. 2017 Nov;83:55-62. doi: 10.1016/j.archoralbio.2017.07.004. Epub 2017 Jul 8.

Abstract

OBJECTIVE

To identify the expression of nonclassical human leukocyte antigen G and E (HLA-G and -E), programmed cell death ligand-1 (PD-L1) and granzyme B (GB) in intraoral mucoepidermoid carcinomas (MECs), and to assess whether such expressions are related to metastasis, survival, staging, tumor grade and number of GB-positive cells.

DESIGN

For this cross-sectional study, samples of MEC (n=30) were selected and classified as low-grade (LG), intermediate-grade (IG) or high-grade (HG), according to the WHO grading system. HLA-G, -E and PD-L1 were identified by immunohistochemistry and quantified as the proportion of positive neoplastic cells. The density of GB+ cells was also evaluated. The Kruskal-Wallis test was used with a 5% significance level.

RESULTS

Expressions of HLA-G, -E and PD-L1 were identified in the majority of epidermoid, intermediate and clear cells, but not in the mucous cells of the MECs. The quantitative analysis of the total percentage of positive neoplastic cells showed overexpression of this set of proteins in all MEC samples. The expression of these proteins and histological grading were positively correlated [HLA-G (LG=79% positive cells, IG=96%, HG=99%; p=0.0004), HLA-E (LG=70%, IG=96%, HG=99%; p<0.0001) and PD-L1 (LG=34%, IG=79%, HG=80%; p=0.01)]. No relationship was observed between the immunosuppressive proteins and other clinicopathological parameters. Low GB density was found in all MEC samples.

CONCLUSIONS

The augmented expression of HLA-G, -E and PD-L1 in the intraoral MEC might suggest a role of these molecules in the scape of neoplastic cells from immunosurveillance.

摘要

目的

鉴定非经典人类白细胞抗原 G 和 E(HLA-G 和 -E)、程序性细胞死亡配体 1(PD-L1)和颗粒酶 B(GB)在口腔黏膜表皮样癌(MEC)中的表达,并评估这些表达是否与转移、生存、分期、肿瘤分级和 GB 阳性细胞数量有关。

设计

在这项横断面研究中,根据世界卫生组织(WHO)分级系统,选择并分类了 30 例 MEC 样本为低级别(LG)、中级别(IG)或高级别(HG)。通过免疫组织化学鉴定 HLA-G、-E 和 PD-L1,并将阳性肿瘤细胞的比例量化。还评估了 GB+细胞的密度。采用 Kruskal-Wallis 检验,以 5%的显著性水平进行分析。

结果

在表皮样、中间和透明细胞中鉴定出 HLA-G、-E 和 PD-L1 的表达,但在 MEC 的黏液细胞中没有。对阳性肿瘤细胞总数百分比的定量分析显示,所有 MEC 样本均存在这组蛋白的过表达。这些蛋白的表达与组织学分级呈正相关[HLA-G(LG 阳性细胞比例为 79%,IG 为 96%,HG 为 99%;p=0.0004),HLA-E(LG 为 70%,IG 为 96%,HG 为 99%;p<0.0001)和 PD-L1(LG 为 34%,IG 为 79%,HG 为 80%;p=0.01)]。免疫抑制蛋白与其他临床病理参数之间未见相关性。在所有 MEC 样本中均发现 GB 密度较低。

结论

口腔黏膜表皮样癌中 HLA-G、-E 和 PD-L1 的表达增强可能表明这些分子在肿瘤细胞逃避免疫监视中的作用。

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