Ichihara T, Sakamoto J, Nakao A, Furukawa K, Watanabe T, Suzuki N, Horisawa M, Nagura H, Lloyd K O, Takagi H
Department of Surgery, National Nagoya Hospital, Japan.
Cancer. 1993 Jan 1;71(1):71-81. doi: 10.1002/1097-0142(19930101)71:1<71::aid-cncr2820710113>3.0.co;2-4.
Seven murine monoclonal antibodies (MoAb) detecting blood group antigens of the Lewis system and their sialylated derivatives were used to define their immunohistochemical distribution in normal and malignant pancreatic tissues. The specific blood group antigens studied included Lewis(a) (Le(a)), Lewisb (Leb), Lewisx (Le(x)), Lewis(y) (Le(y)), sialyl-Lewis(a) (s-Le(a)), sialyl-lacto-N-tetraose (s-LNT), and sialyl-Lewisx (s-Le(x)).
The expression of these antigens was analyzed by immunoperoxidase technique in pancreatic tissue of patients with (n = 27) and without (n = 19) pancreatic cancer. The genetic background of their secretor status and their Lewis phenotypes were determined by the enzyme-linked immunosorbent assay using purified salivary glycoprotein and MoAb against eight different blood group-related antigens (Le(a), Leb, Le(x), Le(y), H1, H2, A, B2), and the putative genotypes of the patients were classified as follows: SeLe, Sele, seLe, and sele.
The following results were obtained: (1) In normal pancreas, Le(a), s-Le(a), s-LNT, and s-Le(x) were expressed in ducts, but their expression was restricted to the luminal side of the cytoplasm (cytoplasmic type with positive polarity). Leb and Le(y) showed similar patterns of expression in ducts and some parts of the acinus. In contrast, Le(x) was absent in most cases. (2) Expression of Leb was observed in normal pancreatic ducts in all 46 patients, regardless of their genotypes. Le(a) and s-Le(a) were not expressed in specimens from patients with the seLe and sele saliva phenotypes. (3) In pancreatic cancer, the following antigens were expressed cytoplasmically in the proportion of cases indicated: Le(a) (78%), Leb (85%), Le(x) (33%), Le(y) (44%), s-Le(a) (78%), s-LNT (89%), and s-Le(x) (85%). They also were detected in the surrounding stroma. This pattern of expression is distinct from that found in normal pancreatic tissue. Patients with Sele and sele genotypes did not express Le(a) or s-Le(a), except in one case. (4) Serum levels of carbohydrate antigen 19-9 (CA 19-9) were not elevated in patients with pancreatic cancer with the Sele and sele genotypes but were elevated in most patients with SeLe and seLe genotypes.
The overall findings indicate that Lewis-related antigens act as pancreatic tissue-related antigens, depending in part on salivary phenotypes of the patient. With proper antigen selection and the determination of secretor status, these anti-blood group MoAb may be of clinical utility in the diagnosis of pancreatic cancer.
使用七种检测刘易斯系统血型抗原及其唾液酸化衍生物的鼠单克隆抗体（MoAb）来确定它们在正常和恶性胰腺组织中的免疫组织化学分布。所研究的特定血型抗原包括刘易斯（a）（Le（a））、刘易斯b（Leb）、刘易斯x（Le（x））、刘易斯y（Le（y））、唾液酸化刘易斯（a）（s-Le（a））、唾液酸化乳糖-N-四糖（s-LNT）和唾液酸化刘易斯x（s-Le（x））。
采用免疫过氧化物酶技术分析27例胰腺癌患者和19例非胰腺癌患者胰腺组织中这些抗原的表达。通过酶联免疫吸附测定法，使用纯化的唾液糖蛋白和针对八种不同血型相关抗原（Le（a）、Leb、Le（x）、Le（y）、H1、H2、A、B2）的MoAb来确定其分泌状态的遗传背景及其刘易斯表型，患者的假定基因型分类如下：SeLe、Sele、seLe和sele。
获得了以下结果：（1）在正常胰腺中，Le（a）、s-Le（a）、s-LNT和s-Le（x）在导管中表达，但其表达仅限于细胞质的腔侧（具有正极性的细胞质类型）。Leb和Le（y）在导管和腺泡的某些部分表现出相似的表达模式。相比之下，大多数情况下不存在Le（x）。（2）在所有46例患者的正常胰腺导管中均观察到Leb的表达，无论其基因型如何。Le（a）和s-Le（a）在具有seLe和sele唾液表型的患者标本中未表达。（3）在胰腺癌中，以下抗原在所示病例比例中呈细胞质表达：Le（a）（78%）、Leb（85%）、Le（x）（33%）、Le（y）（44%）、s-Le（a）（78%）、s-LNT（89%）和s-Le（x）（85%）。它们也在周围基质中被检测到。这种表达模式与正常胰腺组织中的不同。具有Sele和sele基因型的患者除1例例外均未表达Le（a）或s-Le（a）。（4）具有Sele和sele基因型的胰腺癌患者血清中糖类抗原19-9（CA 19-9）水平未升高，但大多数具有SeLe和seLe基因型的患者血清中该水平升高。
总体研究结果表明，刘易斯相关抗原作为胰腺组织相关抗原，部分取决于患者的唾液表型。通过适当选择抗原和确定分泌状态，这些抗血型MoAb可能在胰腺癌诊断中具有临床应用价值。
