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黏蛋白特异性单克隆抗体和凝集素在妇科癌症肿瘤相关血清标志物检测中的应用

The use of mucin-specific monoclonal antibodies and lectins in the detection of tumor-associated serum markers in gynecological cancer.

作者信息

Devine P L, McGuckin M A, Ramm L E, Harada H, Ward B G

机构信息

Department of Obstetrics & Gynaecology, University of Queensland, Royal Brisbane Hospital, Australia.

出版信息

Cancer Biochem Biophys. 1993 Sep;13(4):221-38.

PMID:8521372
Abstract

The use of the mucin-specific lectin from Sambucus sieboldiana (SSAM) in the detection of tumor-associated serum antigens produced by patients with ovarian, cervical, and uterine cancer was investigated. Two-site assays were developed which used either SSAM or the MUC1 core protein-specific monoclonal antibody (mab) BC2 as capture, and biotinylated SSAM to detect bound mucin (SSAM and BC2SSAM assays respectively). These new assays were compared to the CA125 assay, and another assay for MUC1 (CASA), which utilizes the core protein reactive mabs BC2 and BC3. some asymptomatic women and patients with benign disease showed very high levels in the SSAM assay, while this was not the case in the other assays. When cutoff levels were set to exclude healthy women and patients with benign disease, the levels of detection in patients with ovarian cancer were 51% with CASA (> 6.7 units/ml), 71% with CA125 (> 250 units/ml), and 38% with BC2SSAM (> 8.6 units/ml). The levels of detection in cervical and uterine cancer patients were 28% and 25% with CASA, 0% and 8% with CA125, and 28% and 25% with BC2SSAM respectively. Of particular interest was the very different spectrum of reactivity observed with the CASA and BC2SSAM assays which use the same capture mab, indicating that each assay detects different glycoforms of the MUC1 mucin. Indeed, when used in combination, the CASA and BC2SSAM assays gave 62% of ovarian cancer patients, and 50% of cervical or uterine cancer patients with elevated marker levels. The additional use of BC2SSAM gave no advantage over the combined use of the CASA and CA125 assays in ovarian cancer, with 80% of patients detected, but the CASA/BC2SSAM combination was particularly useful in the cervical and uterine cancers due to the low level of detection with CA125. In fact, the additional use of CA125 gave no advantage over the CASA/BC2SSAM combination in these patients. Furthermore, the BC2SSAM assay may also be useful in monitoring patients with high preoperative BC2SSAM levels (> 10 units/ml), since this assay predicted recurrence in 5/5 cases, and was negative in all cases with no evidence of disease. Furthermore, the performance of this assay in monitoring these patients was equal or superior to CA125 and CASA.

摘要

研究了接骨木(Sambucus sieboldiana,SSAM)中粘蛋白特异性凝集素在检测卵巢癌、宫颈癌和子宫癌患者产生的肿瘤相关血清抗原中的应用。开发了两种双位点检测方法,一种使用SSAM作为捕获剂,另一种使用MUC1核心蛋白特异性单克隆抗体(mab)BC2作为捕获剂,并用生物素化的SSAM检测结合的粘蛋白(分别为SSAM检测法和BC2SSAM检测法)。将这些新检测方法与CA125检测法以及另一种检测MUC1的方法(CASA)进行比较,CASA检测法使用核心蛋白反应性单克隆抗体BC2和BC3。一些无症状女性和良性疾病患者在SSAM检测法中显示出非常高的水平,而在其他检测法中并非如此。当设定临界值以排除健康女性和良性疾病患者时,卵巢癌患者中CASA检测法(>6.7单位/毫升)的检测率为51%,CA125检测法(>250单位/毫升)的检测率为71%,BC2SSAM检测法(>8.6单位/毫升)的检测率为38%。宫颈癌和子宫癌患者中CASA检测法的检测率分别为28%和25%,CA125检测法的检测率分别为0%和8%,BC2SSAM检测法的检测率分别为28%和25%。特别有趣的是,使用相同捕获单克隆抗体的CASA检测法和BC2SSAM检测法观察到的反应谱非常不同,这表明每种检测法检测的是MUC1粘蛋白的不同糖型。实际上,联合使用CASA检测法和BC2SSAM检测法时,62%的卵巢癌患者以及50%的宫颈癌或子宫癌患者标志物水平升高。在卵巢癌中,额外使用BC2SSAM检测法相比联合使用CASA检测法和CA125检测法并无优势,后者能检测出80%的患者,但CASA/BC2SSAM联合检测法在宫颈癌和子宫癌中特别有用,因为CA125检测法的检测率较低。事实上,在这些患者中额外使用CA125检测法相比CASA/BC2SSAM联合检测法并无优势。此外,BC2SSAM检测法对于术前BC2SSAM水平较高(>10单位/毫升)的患者的监测可能也有用,因为该检测法在5/5例病例中预测了复发,且在所有无疾病证据的病例中均为阴性。此外,该检测法在监测这些患者方面的表现与CA125检测法和CASA检测法相当或更优。

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