Kim Y S, Itzkowitz S H, Yuan M, Chung Y, Satake K, Umeyama K, Hakomori S
Gastrointestinal Research Laboratory, Veterans Administration Medical Center, San Francisco, California 94121.
Cancer Res. 1988 Jan 15;48(2):475-82.
Carbohydrate antigens are useful markers for the serological detection of pancreatic cancer. However, data concerning the expression of structurally well-defined carbohydrate antigens in normal and malignant pancreatic tissue is quite limited. The Lex and Leg antigens are closely related carbohydrate antigens synthesized on type 2 blood group oligosaccharide side chains of glycolipids and glycoproteins. Monoclonal antibodies anti-SSEA-1 and AH6 recognize "simple" Lex and Ley epitopes, respectively, regardless of the length of the carrier carbohydrate. Other monoclonal antibodies recognize Lex (FH4), sialyl Lex (FH6, IB9) or Ley (KH1, CC-1, CC-2) carried only by elongated type 2 side chains with or without internal alpha 1,3 fucosyl substitution. The present comparative immunohistochemical study used tissues of normal pancreas, chronic pancreatitis, and pancreatic cancer to determine the normal expression of Lex and Ley antigens in the pancreas and to elucidate any cancer-associated alterations. Lex-related antigens were not expressed in normal pancreas, expressed in only 10-20% of chronic pancreatitis tissues, but expressed in 50-70% of pancreatic cancer tissues. The frequency of Lex-related antigen expression in pancreatic cancer tissues was lowest in poorly differentiated cancers. Within a given specimen, at least three or all four of the Lex recognizing monoclonal antibodies were simultaneously expressed. Unlike Lex antigens, Ley-related antigens were expressed in 32-77% of specimens of normal pancreas, with similar frequencies in specimens of chronic pancreatitis and pancreatic cancer. In normal pancreas, simple Ley was expressed by both ductal and acinar cells, but extended Ley antigens were expressed only by acinar cells. In pancreatic cancer, extended Ley antigen expression was found in less than 10% of poorly differentiated tumors. Coexpression among the Ley-related antigens was less common than with the Lex-related antigens. Also in cancer specimens, simple Lex and simple Lex antigens were often concordantly expressed, whereas extended Lex and extended Ley antigen expression was often discordant. Hyperplastic ducts and ductules associated with pancreatic cancer expressed Lex-related antigens more frequently than morphologically similar lesions associated with chronic pancreatitis. These results demonstrate that Lex-related antigens are cancer-associated determinants in the human pancreas. The discrepant expression between Lex and Ley antigens in these tissues implies altered regulation of fucosyltransferase activity associated with the malignant state.
碳水化合物抗原是用于胰腺癌血清学检测的有用标志物。然而，关于结构明确的碳水化合物抗原在正常和恶性胰腺组织中的表达数据相当有限。Lex和Ley抗原是在糖脂和糖蛋白的2型血型寡糖侧链上合成的密切相关的碳水化合物抗原。抗SSEA - 1和AH6单克隆抗体分别识别“简单”的Lex和Ley表位，而不考虑载体碳水化合物的长度。其他单克隆抗体识别仅由带有或不带有内部α1,3岩藻糖基取代的延长型2侧链携带的Lex（FH4）、唾液酸化Lex（FH6、IB9）或Ley（KH1、CC - 1、CC - 2）。本比较免疫组织化学研究使用正常胰腺、慢性胰腺炎和胰腺癌组织来确定Lex和Ley抗原在胰腺中的正常表达，并阐明任何与癌症相关的改变。Lex相关抗原在正常胰腺中不表达，仅在10 - 20%的慢性胰腺炎组织中表达，但在50 - 70%的胰腺癌组织中表达。胰腺癌组织中Lex相关抗原表达频率在低分化癌中最低。在给定标本中，至少三种或全部四种识别Lex的单克隆抗体同时表达。与Lex抗原不同，Ley相关抗原在32 - 77%的正常胰腺标本中表达，在慢性胰腺炎和胰腺癌标本中的频率相似。在正常胰腺中，简单Ley由导管和腺泡细胞表达，但延长型Ley抗原仅由腺泡细胞表达。在胰腺癌中，延长型Ley抗原表达在不到10%的低分化肿瘤中发现。Ley相关抗原之间的共表达比Lex相关抗原少见。在癌症标本中，简单Lex和简单Ley抗原也经常一致表达，而延长型Lex和延长型Ley抗原表达经常不一致。与胰腺癌相关的增生性导管和小导管比与慢性胰腺炎相关的形态学相似病变更频繁地表达Lex相关抗原。这些结果表明Lex相关抗原是人类胰腺中与癌症相关的决定因素。这些组织中Lex和Ley抗原的差异表达意味着与恶性状态相关的岩藻糖基转移酶活性调节改变。
