Itzkowitz S H, Yuan M, Fukushi Y, Lee H, Shi Z R, Zurawski V, Hakomori S, Kim Y S
Gastrointestinal Research Laboratory, Veterans Administration Medical Center, San Francisco, CA 94121.
Cancer Res. 1988 Jul 1;48(13):3834-42.
The CA 19-9 antigen is a monosialosyl Lea blood group antigen which has been shown to be a useful tumor-associated antigen for the diagnosis of gastrointestinal cancers. Recently, a sialylated derivative of this antigen, disialosyl Lea, was isolated from a colon cancer liver metastasis and a monoclonal antibody (FH7) recognizing this novel determinant was developed. The present study simultaneously compared the expression of Lea, monosialosyl Lea, and disialosyl Lea antigens in a variety of nonmalignant, premalignant, and malignant tissues of the colorectum and pancreas with an aim toward elucidating whether disialosyl Lea is expressed as a tumor-associated antigen. In normal colonic mucosa, disialosyl Lea expression closely resembled Lea expression in overall frequency, segmental distribution, and cellular localization whereas monosialosyl Lea (CA 19-9) was essentially absent. Along the crypt axis, Lea was more often expressed in goblet cells of the upper crypt whereas disialosyl Lea was found in goblet cells along the entire crypt. Fetal colonic mucosa expressed all three antigens, as did most colorectal cancers regardless of location within the colon or degree of differentiation. The majority of hyperplastic polyps and practically all adenomatous polyps also expressed these three antigens, and in adenomas, antigen expression was independent of polyp size, villous morphology, or degree of dysplasia. In the normal pancreas, the three antigens were expressed on ductal, ductular and centroacinar cells of all specimens. The majority of pancreatic cancers expressed all three antigens. Thus, in the normal colon, the absence of monosialosyl Lea (CA 19-9) in the presence of disialosyl Lea suggests that an alpha 2,6 sialyltransferase is active, which results in the masking of CA 19-9 antigen expression. These results further support the concept that specific sialyltransferases play a role in regulating the expression of tumor-associated antigens.
CA 19-9抗原是一种单唾液酸化Lea血型抗原，已被证明是用于诊断胃肠道癌症的一种有用的肿瘤相关抗原。最近，从结肠癌肝转移灶中分离出了该抗原的一种唾液酸化衍生物——双唾液酸化Lea，并研制出了识别这种新决定簇的单克隆抗体（FH7）。本研究同时比较了Lea、单唾液酸化Lea和双唾液酸化Lea抗原在结直肠和胰腺的各种非恶性、癌前和恶性组织中的表达，旨在阐明双唾液酸化Lea是否作为肿瘤相关抗原表达。在正常结肠黏膜中，双唾液酸化Lea的表达在总体频率、节段分布和细胞定位方面与Lea的表达非常相似，而单唾液酸化Lea（CA 19-9）基本不存在。沿着隐窝轴，Lea更常在上部隐窝的杯状细胞中表达，而双唾液酸化Lea则在整个隐窝的杯状细胞中发现。胎儿结肠黏膜表达所有三种抗原，大多数结直肠癌也表达，无论其在结肠内的位置或分化程度如何。大多数增生性息肉和几乎所有腺瘤性息肉也表达这三种抗原，在腺瘤中，抗原表达与息肉大小、绒毛形态或发育异常程度无关。在正常胰腺中，所有标本的导管、小导管和中央腺泡细胞上均表达这三种抗原。大多数胰腺癌表达所有三种抗原。因此，在正常结肠中，存在双唾液酸化Lea时单唾液酸化Lea（CA 19-9）的缺失表明α2,6唾液酸转移酶是活跃的，这导致了CA 19-9抗原表达的掩盖。这些结果进一步支持了特定唾液酸转移酶在调节肿瘤相关抗原表达中起作用的概念。
