SENSITIVE AND SPECIFIC MONOCLONAL-ANTIBODY RECOGNITION OF HUMAN-LUNG CANCER ANTIGEN ON PRESERVED SPUTUM CELLS - A NEW APPROACH TO EARLY LUNG-CANCER DETECTION
SENSITIVE AND SPECIFIC MONOCLONAL-ANTIBODY RECOGNITION OF HUMAN-LUNG CANCER ANTIGEN ON PRESERVED SPUTUM CELLS - A NEW APPROACH TO EARLY LUNG-CANCER DETECTION
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DOI：
10.1200/jco.1988.6.11.1685
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发表时间：
1988-11-01
影响因子：
45.3
通讯作者：
MULSHINE, JL
中科院分区：
文献类型：
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作者：
TOCKMAN, MS;GUPTA, PK;MULSHINE, JL
应用抗小细胞糖脂抗原(SCC)和非小细胞肺癌蛋白抗原(NSCC)的鼠单抗(MAb)对参加约翰霍普金斯肺脏计划(JHLP)的人的痰标本进行保存。在1973年开展的这项评估痰细胞学筛查效果的研究中，一半的高危参与者(5226名男性)。45岁，目前吸烟.gtoreq.每天1包香烟)，随机抽取标本进行细胞病理学分析。在接下来的5到8年的定期筛查中，626人(12%)表现出中度(或更高)的非典型性。其中69人(26人进展到癌症，43人没有)在本研究中被随机选择进行盲法改良的单抗免疫染色方案。在22例最终进展为癌症的患者中，14例具有满意的形态异型性(敏感性%)，而在40例未进展为肺癌的患者中，35例为无反应(特异性88%)。对真阳性标本(14/22例非典型性肺炎)的复习显示，它们是在诊断前24个月收集的。相比之下，8/22的假阴性非典型性(染色失败)显示它们在被诊断为癌症之前平均收集了57个月。随后的样本(平均在癌症出现前26个月)，来自最初被认为是“假阴性”的参与者的样本确实染色呈阳性，在肺癌临床出现前平均2年收集的样本中，敏感性提高到91%。特异度保持在88%。在肺癌的预防、检测和治疗研究中，提前2年识别肿瘤抗原的表达可能是一个有价值的中间终点。
Murine monoclonal antibodies (Mabs) to a glycolipid antigen of small-cell (SCC) and a protein antigen of non-small-cell lung cancer (NSCC) were applied to preserved sputum specimens from individuals who participated in The Johns Hopkins Lung Project (JHLP). In that study, undertaken in 1973 to evaluate the efficacy of sputum cytology screening, half of the high-risk participants (5,226 men .gtoreq. 45 years of age, currently smoking .gtoreq. 1 pack of cigarettes per day) were randomly assigned to produce specimens for cytopathological analysis. During regular screenings over the next 5 to 8 years, 626 (12%) showed moderate (orgreater) atypia. Sixty-nine of these (26 who progerssed to cancer, 43 who did not) were randomly selected for a blinded improved Mab immunostaining protocol in the present study. Satisfactory specimens with morphologic atypia immunostained positively in 14 of the 22 patients who eventually progressed to cancer (sensitivity 64%), and were nonreactive in 35 of the 40 patients who did not progress to lung cancer (specificity 88%). Review of the true positive specimens (14/22 atypias) showed that they were collected 24 months in advance of diagnosis. In contrast, the 8/22 false negative atypias (failure to stain) showed that they were collected for an average of 57 months preceding the diagnosis of concer. Subsequent specimens (average, 26 months before cancer), from participants who were originally considered "false negative" did stain positively, improving sensitivity to 91% among specimens collected for an average of 2 years in advance of the clincal appearance of lung cancer. Specificity remained at 88%. Recognition of neoplastic antigen expression 2 years in advance of clinical cancer may be a valuable intermediate end point in studies of lung cancer prevention, detection, and therapy.