Applications of monoclonal antibodies in clinical cytology as exemplified by studies with monoclonal antibody B72.3. The George N. Papanicolaou award lecture.
Applications of monoclonal antibodies in clinical cytology as exemplified by studies with monoclonal antibody B72.3. The George N. Papanicolaou award lecture.
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单克隆抗体在临床细胞学中的应用，以单克隆抗体 B72.3 的研究为例。
作者：
W. Johnston
单抗(MAb)B72.3与一种名为Tag-72的大分子糖蛋白肿瘤相关抗原发生反应，此前已被证明与卵巢、结肠癌和乳房腺癌的福尔马林固定、石蜡包埋组织切片有反应，但不与各种正常成人组织反应。它已被证明是一种免疫细胞化学辅助手段，用于诊断人浆膜积液的细胞块和细胞离心剂中的癌症，对肿瘤细胞(尤其是腺癌)具有选择性反应，高于反应性间皮细胞。应用免疫组织化学ABC法和福尔马林固定石蜡包埋细胞悬液，检测21例乳腺腺癌患者胸腔积液中的肿瘤细胞。41例良性胸腔积液中，所有细胞类型均未见反应性。相反，单抗B72.3对白血病或淋巴瘤积液，或恶性积液的间皮细胞无反应。在12例肺腺癌和16例卵巢腺癌患者的胸腔积液标本中，MAb B72.3也检测到腺癌细胞。单抗B72.3最近已用于细针吸取(FNA)活组织标本和相应的手术切除的肿瘤，以确定细胞的反应性。应用ABC免疫组织化学方法，分析细针抽吸物和相应的手术切除肿瘤组织中TAG-72的表达。27例肺腺癌和腺鳞癌、17例乳腺腺癌、6例结肠腺癌及其他部位癌针吸标本中单抗B72.3染色阳性。相比之下，21例肺小细胞癌、13例恶性黑色素瘤、2例淋巴瘤和2例肉瘤未见抗体染色。乳腺、肺、胰腺、腮腺和甲状腺的良性病变也没有染色。在许多患者中，肿瘤组织也已被切除，并可与单抗B72.3进行对比检查。在90%以上的患者中，抽吸物中肿瘤细胞的染色模式被发现可以预测类似手术切除的肿瘤中的抗体反应模式。从这些研究中得出结论，单抗B72.3定义了一种肿瘤相关抗原，它在肿瘤细胞中表达，而在良性细胞中表达，在癌症中最有选择性地表达，可以作为一种新的辅助手段用于诊断胸腔积液和细针活检中的肿瘤。
The monoclonal antibody (MAb) B72.3, reactive with a high-molecular-weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been previously shown to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct for the diagnosis of carcinoma in cell blocks and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from all of 21 patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions from 41 patients. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected adenocarcinoma cells in effusion specimens from 12 of 12 patients with adenocarcinoma of the lung and 16 of 16 patients with adenocarcinoma of the ovary. MAb B72.3 has recently been used with fine needle aspiration (FNA) biopsy specimens and the corresponding surgically excised tumors to determine cellular reactivity. Using the ABC immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumors were analyzed for TAG-72 expression. Positive staining with MAb B72.3 was observed in needle aspirates of 27 of 27 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, 6 of 6 adenocarcinomas of the colon and in carcinomas from other body sites. In contrast, 21 small-cell carcinomas of the lung, 13 malignant melanomas, 2 lymphomas and 2 sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B72.3. In more than 90% of these patients, the staining patterns of the tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies, it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, that is most selectively expressed in carcinomas and that may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in fine needle aspiration biopsies.