Kim Y S, Yuan M, Itzkowitz S H, Sun Q B, Kaizu T, Palekar A, Trump B F, Hakomori S
Cancer Res. 1986 Nov;46(11):5985-92.
The LeY determinant, a difucosylated type 2 blood group-related antigen, is a positional isomer of the Leb blood group antigen and a fucosylated derivative of the LeX antigen. The LeX antigen behaves like an oncodevelopmental tumor-associated antigen in human colon cancer, and extended polyfucosyl LeX antigens are more specific for colon cancer tissues than are simple, monofucosyl LeX antigens. The present investigation compared the expression of simple and extended LeY antigens in a variety of malignant and nonmalignant human colonic tissues to gain insight into the normal distribution and cancer-associated expression of these antigens. Monoclonal antibody AH-6, which recognizes the LeY epitope irrespective of its carrier carbohydrate chain, stained the majority of specimens regardless of malignant potential or location within the colon. In contrast, CC-1 and CC-2 monoclonal antibodies, which recognize extended LeY structures, and KH-1, which is specific to trifucosyl LeY, preferentially stained malignant colonic tissues and rarely stained normal colonic mucosae. Mucosa immediately adjacent to cancer usually stained with AH-6 but not with KH-1, CC-1, or CC-2. Extended or trifucosyl LeY antigen expression was limited exclusively to premalignant (adenomatous) polyps and was invariably absent from nonpremalignant (hyperplastic) polyps. Moreover, among adenomatous polyps, extended LeY antigen expression tended to correlate with three parameters of malignant potential: larger polyp size; villous histology, and severe dysplasia. AH-6 failed to distinguish between hyperplastic and adenomatous polyps. In second-trimester fetal colonic mucosa, AH-6 bound to both proximal and distal segments whereas KH-1, CC-1, and CC-2 bound only to proximal segments. We conclude that in human colon, the LeY hapten is an oncodevelopmental cancer-associated antigen and extended LeY antigens are highly specific markers for malignancy and premalignancy.
LeY决定簇是一种二岩藻糖基化的2型血型相关抗原，是Leb血型抗原的位置异构体以及LeX抗原的岩藻糖基化衍生物。LeX抗原在人类结肠癌中表现为一种肿瘤发生发展相关的肿瘤相关抗原，与简单的单岩藻糖基LeX抗原相比，延伸的多岩藻糖基LeX抗原对结肠癌组织更具特异性。本研究比较了简单和延伸型LeY抗原在各种恶性和非恶性人类结肠组织中的表达情况，以深入了解这些抗原的正常分布以及与癌症相关的表达。单克隆抗体AH-6，无论其载体碳水化合物链如何，均可识别LeY表位，它能染色大多数标本，而不考虑其恶性潜能或在结肠内的位置。相比之下，识别延伸型LeY结构的CC-1和CC-2单克隆抗体，以及对三岩藻糖基LeY特异的KH-1，优先染色恶性结肠组织，很少染色正常结肠黏膜。紧邻癌症的黏膜通常用AH-6染色，但不用KH-1、CC-1或CC-2染色。延伸型或三岩藻糖基LeY抗原的表达仅局限于癌前（腺瘤性）息肉，非癌前（增生性）息肉中则始终不存在。此外，在腺瘤性息肉中，延伸型LeY抗原的表达往往与恶性潜能的三个参数相关：息肉尺寸较大；绒毛状组织学，以及重度发育异常。AH-6无法区分增生性息肉和腺瘤性息肉。在孕中期胎儿结肠黏膜中，AH-6与近端和远端节段均结合，而KH-1、CC-1和CC-2仅与近端节段结合。我们得出结论，在人类结肠中，LeY半抗原是一种肿瘤发生发展相关的癌症相关抗原，延伸型LeY抗原是恶性和癌前病变的高度特异性标志物。
