CA 125: The past and the future
CA 125: The past and the future
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DOI：
10.1177/172460089801300402
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发表时间：
1998-10-01
影响因子：
2
通讯作者：
Mills, GB
中科院分区：
文献类型：
--
作者：
Bast, RC;Xu, FJ;Mills, GB
在过去的15年里，在了解CA 125测定的潜力和局限性方面取得了实质性进展。CA 125的实验室和临床研究已发表2000多篇论文。最初的CA 125检测使用OC 125抗体，其识别高分子量糖蛋白上的CA 125表位。尽管进行了多次尝试，但编码肽组分的基因尚未被克隆。已针对该分子表达的其他表位产生了单克隆抗体，从而开发了CA 125-II检测试剂盒，该试剂盒显示出较少的日常变化。使用任何一种检测方法，在许多良性疾病中检测到CA 125水平升高，包括子宫内膜异位症。CA 125在上皮性卵巢癌中最一致地升高，但可在许多妇科（子宫内膜、输卵管）和非妇科（胰腺、乳腺、结肠和肺癌）癌症中表达。CA 125检测的最佳应用是监测卵巢癌：在几项多变量分析中，在初次化疗期间CA 125的下降率是一个重要的独立预后因素。在第二次手术监测程序时CA 125持续升高预测残留疾病具有>95%的特异性。在大多数但不是所有研究中，CA 125值升高在临床检测到复发疾病之前至少3个月。考虑到挽救化疗的适度活性，该信息尚未对生存率产生影响。在随后的化疗期间CA 125升高与超过90%的病例中的疾病进展相关。CA 125可作为新药II期临床试验中临床反应的有效替代标志物。CA 125水平可以帮助区分良性和恶性盆腔肿块，允许有效的分流患者进行初次手术。卵巢癌的早期检测仍然是CA 125最有前途的应用。已经开发了一种算法，该算法基于CA 125值的水平和趋势来估计卵巢癌（ROC）的风险。已经启动了一项主要试验，使用ROC算法触发经阴道超声检查和/或随后的剖腹手术。这样的试验可以证明通过早期检测可以改善生存率。这种策略应该提供足够的特异性，但早期疾病的敏感性可能不是最佳的。在未来，可以使用多个标记物和神经网络分析来实现提高的灵敏度。大多数血清肿瘤标志物是蛋白质或碳水化合物，但脂质标志物如溶血磷脂酸值得评估。基因组学和蛋白质组学技术应确定额外的新标记。
Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer: The rate of decline in CA 125 during primary chemotherapy has been art important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with >95% specificity Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125 An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.