Kübel R, Büchler M, Baczako K, Beger H G
Abteilung für Allgemeine Chirurgie, Universität Ulm.
Langenbecks Arch Chir. 1987;371(4):243-52. doi: 10.1007/BF01258972.
Immunhistochemistry using hybridoma-derived monoclonal antibodies (MAb's) directed against tumor associated antigens offers new approaches to morphological diagnosis of tumors, e.g. for classification and typing of tumor subtypes with different prognosis. Before in-vivo application of monoclonal antibodies in man for diagnostic or therapeutic purposes the tissue distribution of the antibody should be determined immunhistochemically for assessment of antibody sensitivity and specificity. The binding capacity of the newly developed MAb BW 494/32 to pancreatic cancer tissues was therefore tested by immunhistochemistry, other benign and malignant intestinal and extraintestinal tissues served as controls. The MAb BW 494/32 showed positive immunoreactivity in all cases of ductal pancreatic adenocarcinomas grading I to II (sensitivity: 100%). In grading III carcinomas the target antigen was only accessible in half of the tested specimens. Specificity was limited by a mostly weak immunoreactivity with normal pancreas tissue in 36%, with acute inflamed tissue in 100%, with inflamed tissue in chronic pancreatitis in 71%. Extrapancreatic specificity was restricted by positive antibody binding to singular goblet cells of gastrointestinal epithelium. The well established antibody CA 19-9 was used for comparison. CA 19-9 showed about the same sensitivity of 88% (BW 494/32: 92%) for ductal pancreatic adenocarcinomas grading I to III. Specificity of CA 19-9, however, was comparable more restricted, as CA 19-9 showed a significant cross-reactivity with other gastrointestinal adenocarcinomas (5 out of 6 colorectal cancers, 3/6 gastric carcinomas, 1/3 carcinomas of the common bile duct), with some extraintestinal cancers (breast 60%, lungs 50%) and with other non-cancerous tissues of intestinal origin. According to the results of this study it is worthwhile to investigate the antibody BW 494/32 for possible applications in experimental immunodiagnosis and -therapy of pancreatic cancer.
使用针对肿瘤相关抗原的杂交瘤衍生单克隆抗体（MAb）进行免疫组织化学为肿瘤的形态学诊断提供了新方法，例如用于对具有不同预后的肿瘤亚型进行分类和分型。在将单克隆抗体用于人体的体内诊断或治疗目的之前，应通过免疫组织化学确定抗体的组织分布，以评估抗体的敏感性和特异性。因此，通过免疫组织化学测试了新开发的单克隆抗体BW 494/32与胰腺癌组织的结合能力，其他良性和恶性肠道及肠道外组织作为对照。单克隆抗体BW 494/32在所有I至II级导管胰腺腺癌病例中均显示出阳性免疫反应性（敏感性：100%）。在III级癌中，仅在一半的测试标本中可检测到靶抗原。特异性受到限制，36%的正常胰腺组织、100%的急性炎症组织、71%的慢性胰腺炎炎症组织大多呈现弱阳性免疫反应。胰腺外的特异性受到限制，因为抗体与胃肠道上皮的单个杯状细胞呈阳性结合。使用成熟的抗体CA 19-9进行比较。CA 19-9对I至III级导管胰腺腺癌的敏感性约为88%（BW 494/32：92%）。然而，CA 19-9的特异性受到更多限制，因为CA 19-9与其他胃肠道腺癌（6例结直肠癌中的5例、6例胃癌中的3例、3例胆总管癌中的1例）、一些肠道外癌症（乳腺癌60%、肺癌50%）以及其他肠道来源的非癌组织存在显著交叉反应。根据本研究结果，值得研究抗体BW 494/32在胰腺癌实验免疫诊断和治疗中的可能应用。
