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新型碳水化合物肿瘤抗原 C2-O-sLe x 在犬胃腺癌中上调。

The novel carbohydrate tumor antigen C2-O-sLe x is upregulated in canine gastric carcinomas.

机构信息

Department of Veterinary Population Medicine, University of Minnesota, St. Paul, Minnesota, USA.

出版信息

Vet Pathol. 2010 May;47(3):455-61. doi: 10.1177/0300985810363700. Epub 2010 Apr 7.

Abstract

Sialyl Lewis x-modified core 2 branched O-glycans (C2-O-sLe(x)) on human leukocytes mediate much higher-affinity adhesion to selectins on activated vascular endothelium than does sialyl Lewis x on other structures. In some canine and human carcinomas, high expression of sLe(x)-decorated carbohydrates has been associated with metastasis and, in humans, a poor prognosis, but detection in canine gastric carcinomas is unreported. The authors hypothesized that these carbohydrates are highly expressed in more malignant types of canine gastric carcinomas, they promote metastasis, and they are associated with a poorer prognosis for dogs. The objectives were to determine the presence and importance of C2-O-sLe(x) expression in canine gastric carcinomas. Routine histological sections of 16 canine gastric carcinomas were categorized on the basis of 3 classification schemes: World Health Organization, Lauren, and Goseki. Serial sections were stained with antibodies directed against C2-O-sLe(x) (CHO-131 monoclonal antibody), cytokeratin (Lu-5 monoclonal antibody), and stains to detect neutral and acid mucins (periodic acid-Schiff and alcian blue). Whereas normal gastric mucosal epithelial cells were negative for C2-O-sLe(x), 56% of the tumors examined were positive for C2-O-sLe(x). Importantly, the majority of more poorly differentiated tumor types had more numerous and larger intensely stained areas of C2-O-sLe(x) expression compared with moderate to well-differentiated tumor types. Signet ring-type carcinomas had markedly higher distribution and intensity of periodic acid-Schiff and alcian blue staining than did tubular carcinomas. These findings suggest that C2-O-sLe(x) is a tumor-associated antigen that may play a role in the invasiveness and metastatic potential of certain types of canine gastric carcinomas.

摘要

唾液酸化路易斯 x 修饰的核心 2 分支 O-糖链(C2-O-sLe(x))在人白细胞上介导与激活的血管内皮上的选择素更高亲和力的黏附,而不是其他结构上的唾液酸化路易斯 x。在一些犬和人类的癌中,高表达 sLe(x) 修饰的碳水化合物与转移有关,并且在人类中与预后不良相关,但在犬胃腺癌中尚未报道。作者假设这些碳水化合物在更恶性的犬胃腺癌中高度表达,它们促进转移,并且与犬的预后不良相关。目的是确定 C2-O-sLe(x) 在犬胃腺癌中的存在和重要性。根据 3 种分类方案:世界卫生组织、Lauren 和 Goseki,对 16 例犬胃腺癌的常规组织学切片进行分类。用针对 C2-O-sLe(x)(CHO-131 单克隆抗体)、细胞角蛋白(Lu-5 单克隆抗体)和中性及酸性粘蛋白检测染色剂(过碘酸-Schiff 和阿利新蓝)的抗体对连续切片进行染色。虽然正常胃黏膜上皮细胞 C2-O-sLe(x) 染色阴性,但检查的 56%的肿瘤 C2-O-sLe(x) 染色阳性。重要的是,与中-高分化肿瘤类型相比,大多数分化程度较差的肿瘤类型具有更多数量和更大强度的 C2-O-sLe(x) 表达区域。印戒细胞癌的过碘酸-Schiff 和阿利新蓝染色分布和强度明显高于管状癌。这些发现表明 C2-O-sLe(x) 是一种肿瘤相关抗原,可能在某些类型的犬胃腺癌的侵袭性和转移潜能中发挥作用。

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