Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma

Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma
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S1 单克隆抗体识别的硫酸聚糖可作为恶性胸膜间皮瘤的诊断标志物

DOI:
10.1007/s00408-022-00531-4
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发表时间:
2022
期刊:
影响因子:
5
通讯作者:
Motohiro Kobayashi
Motohiro Kobayashi
中科院分区:
医学3区
文献类型:
--
作者:
Koki Nakashima;Yasuhiro Sakai;Hitomi Hoshino;Yukihiro Umeda;Hiroto Kawashima;Yoshitaka Sekido;Tamotsu Ishizuka;Motohiro Kobayashi

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目的恶性胸膜间皮瘤(MPM)是一种因接触石棉而引起的胸膜恶性肿瘤。对于MPM的诊断,建议使用多个标记物的免疫组织化学以排除鉴别诊断,如肺腺癌。然而,目前使用的标记物的特异性并不完全令人满意。我们之前开发了一种名为S1的单抗,它可以识别6-磺基唾液酸基Lewis x,这是一种表达在高内皮微静脉上的L-选择素配体。在筛选过程中,我们发现该抗体染色正常的胸膜间皮细胞。为了验证这一假设,我们用S1抗体对22例人 组织和25例肺腺癌组织进行了免疫组织化学染色。结果77.3%的 组织为S1阳性,如果局限于上皮样型,阳性率为100%,而肺腺癌组织的阳性率仅为36.0%。统计分析显示,每种疾病之间的S1阳性率有显著差异。此外,用一系列抗糖抗体结合糖苷酶消化的免疫组织化学显示,在MPM中表达的硫酸多糖的结构是6-磺基唾液酸乙酰乳糖胺附着在核心2-支链O-糖链上。结论S1糖表位可作为MPM的新的诊断标志。
PurposeMalignant pleural mesothelioma (MPM) is a malignant neoplasm of the pleura caused by asbestos exposure. For diagnosis of MPM, immunohistochemistry using multiple markers is recommended to rule out differential diagnoses, such as pulmonary adenocarcinoma. However, the specificity of currently used markers is not fully satisfactory. We previously developed a monoclonal antibody named S1, which recognizes 6-sulfo sialyl Lewis x, an L-selectin ligand expressed on high endothelial venules. During the screening process, we discovered that this antibody stained normal pleural mesothelium. This finding prompted us to hypothesize that the epitope recognized by S1 might serve as a new diagnostic marker for MPM.MethodsTo test this hypothesis, we immunostained human MPM (n= 22) and lung adenocarcinoma (n= 25) tissues using S1 antibody.Results77.3% of MPM were S1 positive, and if limited to epithelioid type, the positivity rate was 100%, while that of lung adenocarcinoma was only 36.0%. Statistical analysis revealed a significant difference in the S1 positivity rate between each disease. Furthermore, immunohistochemistry using a series of anti-carbohydrate antibodies combined with glycosidase digestion revealed the structure of sulfated glycans expressed in MPM to be 6-sulfo sialylN-acetyllactosamine attached to core 2-branchedO-glycans.ConclusionWe propose that the S1 glycoepitope could serve as a new diagnostic marker for MPM.
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