Williams G H, Romanowski P, Morris L, Madine M, Mills A D, Stoeber K, Marr J, Laskey R A, Coleman N
Wellcome Trust/Cancer Research Campaign Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14932-7. doi: 10.1073/pnas.95.25.14932.
Carcinoma of the cervix is one of the most common malignancies. Papanicolaou (Pap) smear tests have reduced mortality by up to 70%. Nevertheless their interpretation is notoriously difficult with high false-negative rates and frequently fatal consequences. We have addressed this problem by using affinity-purified antibodies against human proteins that regulate DNA replication, namely Cdc6 and Mcm5. These antibodies were applied to sections and smears of normal and diseased uterine cervix by using immunoperoxidase or immunofluorescence to detect abnormal precursor malignant cells. Antibodies against Cdc6 and Mcm5 stain abnormal cells in cervical smears and sections with remarkably high specificity and sensitivity. Proliferation markers Ki-67 and proliferating cell nuclear antigen are much less effective. The majority of abnormal precursor malignant cells are stained in both low-grade and high-grade squamous intraepithelial lesions. Immunostaining of cervical smears can be combined with the conventional Pap stain so that all the morphological information from the conventional method is conserved. Thus antibodies against proteins that regulate DNA replication can reduce the high false-negative rate of the Pap smear test and may facilitate mass automated screening.
宫颈癌是最常见的恶性肿瘤之一。巴氏涂片检查已使死亡率降低了70%。然而，其解读 notoriously difficult，假阴性率高，且常常导致致命后果。我们通过使用针对调节DNA复制的人类蛋白质（即Cdc6和Mcm5）的亲和纯化抗体来解决这个问题。这些抗体通过免疫过氧化物酶或免疫荧光法应用于正常和患病子宫颈的切片及涂片，以检测异常的恶性前体细胞。针对Cdc6和Mcm5的抗体对宫颈涂片和切片中的异常细胞染色具有非常高的特异性和敏感性。增殖标志物Ki-67和增殖细胞核抗原的效果则差得多。大多数异常的恶性前体细胞在低级别和高级别鳞状上皮内病变中均被染色。宫颈涂片的免疫染色可与传统巴氏染色相结合，从而保留传统方法的所有形态学信息。因此，针对调节DNA复制的蛋白质的抗体可降低巴氏涂片检查的高假阴性率，并可能有助于大规模自动化筛查。
