Yuan M, Itzkowitz S H, Ferrell L D, Fukushi Y, Palekar A, Hakomori S, Kim Y S
J Natl Cancer Inst. 1987 Mar;78(3):479-88.
The LewisX (LeX) antigen [characterized by trisaccharide Gal beta 1----4 (Fuc alpha 1----3)N-acetylglucosamine] is an oncodevelopmental antigen in the human colon. Monoclonal antibodies (MoAbs), anti-SSEA-1 and AH8-183, which recognize LeX antigen either on short oligosaccharide side chains or as a terminal immunodeterminant on longer carbohydrate side chains of glycoconjugates, bind to most colon cancer tissues but also to some normal colon mucosae. However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa. In the present study, these MoAbs were used to compare the expression of various LeX-related antigens in premalignant (adenomatous) and nonpremalignant (hyperplastic) colorectal polyps. Antigen expression in polyps was also compared to antigen expressions of normal colon mucosa and colon cancer tissues. The four MoAbs recognizing extended LeX antigens bound to adenomatous polyps (APs) significantly more than to hyperplastic polyps (HPs). In contrast, anti-SSEA-1 and AH8-183 recognizing monofucosyl LeX were less able to distinguish between APs and HPs. In APs, staining with the four MoAbs recognizing extended LeX antigens correlated with the premalignant parameters of larger polyp size, more severe dysplasia, and increased villose component. However, staining with AH8-183 correlated only with polyp size, and anti-SSEA-1 correlated only with polyp size and degree of dysplasia. In general, the staining frequency of HPs was similar to that of normal colon mucosa, although FH6, which did not stain any specimens of normal mucosa, stained a few HPs. The staining frequency of APs was less than that of colon cancer tissues, but these differences were generally not statistically significant. In conclusion, extended LeX antigens and their sialylated derivatives are cancer-associated antigens that are expressed preferentially in premalignant colon polyps, that tend to correlate with malignant potential in these polyps, and that may eventually help to define mechanisms involved in the polyp-to-cancer sequence.
LewisX（LeX）抗原[由三糖半乳糖β1----4（岩藻糖α1----3）N-乙酰葡糖胺表征]是人类结肠中的一种肿瘤发育抗原。单克隆抗体（MoAbs），抗SSEA-1和AH8-183，它们识别短寡糖侧链上的LeX抗原或作为糖缀合物较长碳水化合物侧链上的末端免疫决定簇，可与大多数结肠癌组织结合，但也可与一些正常结肠黏膜结合。然而，识别扩展的二岩藻糖基化和三岩藻糖基化LeX结构或其唾液酸化衍生物的单克隆抗体FH1、FH4、FH6和IB9与癌症的相关性更强，因为它们很少与正常结肠黏膜结合。在本研究中，这些单克隆抗体被用于比较癌前（腺瘤性）和非癌前（增生性）大肠息肉中各种LeX相关抗原的表达。还将息肉中的抗原表达与正常结肠黏膜和结肠癌组织的抗原表达进行了比较。识别扩展LeX抗原的四种单克隆抗体与腺瘤性息肉（APs）的结合显著多于增生性息肉（HPs）。相比之下，识别单岩藻糖基LeX的抗SSEA-1和AH8-183区分APs和HPs的能力较弱。在APs中，用识别扩展LeX抗原的四种单克隆抗体染色与息肉较大、发育异常更严重和绒毛成分增加等癌前参数相关。然而，用AH8-183染色仅与息肉大小相关，而抗SSEA-1仅与息肉大小和发育异常程度相关。一般来说，HPs的染色频率与正常结肠黏膜相似，尽管不染色任何正常黏膜标本的FH6染色了一些HPs。APs的染色频率低于结肠癌组织，但这些差异通常无统计学意义。总之，扩展的LeX抗原及其唾液酸化衍生物是与癌症相关的抗原，它们优先在癌前结肠息肉中表达，往往与这些息肉的恶性潜能相关，最终可能有助于确定息肉向癌症转变过程中涉及的机制。
