Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer.
Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer.
复制标题
DOI：
--
复制
发表时间：
1989
期刊：
影响因子：
11.2
通讯作者：
S. Itzkowitz;M. Yuan;C. Montgomery;T. Kjeldsen;H. Takahashi;W. Bigbee;Y. Kim
中科院分区：
文献类型：
--
作者：
S. Itzkowitz;M. Yuan;C. Montgomery;T. Kjeldsen;H. Takahashi;W. Bigbee;Y. Kim
粘蛋白糖蛋白是结肠的主要分泌产物，并且含有在多肽主链上合成的O-连接的寡糖。合成O-连接寡糖的初始步骤是将N-乙酰半乳糖胺添加到丝氨酸或苏氨酸残基上，形成Tn抗原。然后，该物质可以接受额外的碳水化合物残基，如唾液酸以形成唾液酸-Tn抗原，或半乳糖以形成T抗原。在结肠中，T抗原是一种肿瘤发育的癌症相关抗原，但对Tn和唾液酸Tn的表达知之甚少。本比较免疫组化研究进行分析这些抗原在胎儿，正常成人，和恶性结直肠组织中的表达，目的是阐明是否Tn和唾液酸-Tn也是肿瘤发育的结肠癌相关抗原，并深入了解结肠细胞中粘蛋白糖基化的最早步骤。我们使用了三种试剂检测Tn抗原（两种单克隆抗体ETn1.01和CU-1，一种凝集素Vicia villosa），两种试剂检测唾液糖基-Tn（单克隆抗体TKH 2和B72.3），一种试剂检测T抗原（单克隆抗体AH 9 -16）。正常结肠粘膜细胞除偶尔与VVA和CU-1反应外，不表达Tn、唾液酸Tn或T抗原。然而，在紧邻癌症的移行粘膜中，所有三种抗原均表达（范围为35%至67%，取决于试剂）。在结肠癌中，表达每种抗原的病例百分比如下：Tn 72- 81%，唾液酸-Tn 93- 96%和T 71%。不像T抗原，这是优先表达的中度良好和分化良好的腺癌，Tn和唾液酸-Tn抗原表达的结肠癌，包括低分化腺癌和粘液（胶体和印戒细胞型）癌的大多数组织学亚群。大多数肿瘤同时表达Tn和唾液酸Tn，通常与T抗原相关。只有一种癌症缺乏所有三种抗原。胎儿结肠粘膜细胞表达所有三种抗原，特别是在杯状细胞粘蛋白。这些结果表明，与T抗原一样，Tn和唾液酸Tn是结肠中的肿瘤发育癌相关抗原。此外，Tn和唾液酸Tn抗原似乎是低分化腺癌和粘液癌的有用标志物：这两种组织学亚群通常不能表达其他癌症相关抗原，并且通常与不良临床结果相关。（400字处截断摘要）
Mucin glycoproteins are major secretory products of the colon and contain O-linked oligosaccharides synthesized on a polypeptide backbone. The initial step in the synthesis of O-linked oligosaccharides is the addition of N-acetylgalactosamine to serine or threonine residues forming the Tn antigen. This substance can then receive additional carbohydrate residues such as sialic acid to form sialosyl-Tn antigen, or galactose to form T antigen. In the colon, the T antigen is an oncodevelopmental cancer-associated antigen but little is known about Tn and sialosyl-Tn expression. The present comparative immunohistochemical study was performed to analyze the expression of these antigens in fetal, normal adult, and malignant colorectal tissues with an aim toward elucidating whether Tn and sialosyl-Tn are also oncodevelopmental colon cancer-associated antigens and to gain insight into the earliest steps of mucin glycosylation in colonocytes. We used three reagents to detect Tn antigen (two monoclonal antibodies ETn1.01 and CU-1, and one lectin Vicia villosa), two reagents to detect sialosyl-Tn (monoclonal antibodies TKH2 and B72.3) and one to detect T antigen (monoclonal antibody AH9-16). Except for occasional reactivity with VVA and CU-1, cells of normal colonic mucosa did not express Tn, sialosyl-Tn, or T antigens. However, in the transitional mucosa immediately adjacent to cancer, all three antigens were expressed (ranging from 35 to 67% of cases depending upon the reagent). In colon cancers, the percentage of cases expressing each antigen were as follows: Tn 72-81%, sialosyl-Tn 93-96%, and T 71%. Unlike T antigen, which was preferentially expressed by moderately well- and well-differentiated adenocarcinomas, both Tn and sialosyl-Tn antigens were expressed by most histological subsets of colon cancers, including poorly differentiated adenocarcinomas and mucinous (colloid and signet ring cell type) carcinomas. The majority of cancers expressed both Tn and sialosyl-Tn, usually in association with T antigen. Only one cancer lacked all three antigens. Fetal colonic mucosal cells expressed all three antigens, particularly in goblet cell mucin. These results indicate that like T antigen, Tn and sialosyl-Tn are oncodevelopmental cancer-associated antigens in the colon. Moreover, Tn and sialosyl-Tn antigens appear to be useful markers of poorly differentiated adenocarcinomas and mucinous carcinomas: two histological subsets that often fail to express other cancer-associated antigens and that are often associated with a poor clinical outcome.(ABSTRACT TRUNCATED AT 400 WORDS)