Linder J
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.
Clin Lab Med. 1990 Mar;10(1):59-76.
An ideal immunohistochemical screening panel would be one in which each antibody is 100% sensitive and specific for the target cell type (e.g., markers for epithelial neoplasms, lymphomas, sarcomas, etc.). Anyone who has practiced immunochemistry is well aware that this situation does not exist. High sensitivity is hindered by the loss of key antigens through formalin fixation and routine tissue processing. Although sensitivity can be improved by dealing with fresh-frozen, lyophilized, or plastic-embedded specimens, these procedures are often perceived as inconvenient by pathologists. Specificity is a more insidious problem. With the advent of monoclonal antibody technology, many individuals equated the monospecificity (e.g., marking one antigen a determinant) with tissue specificity. This, of course, is not the case as determinants recognized by one monoclonal antibody may be expressed on cells of different lineage. High sensitivity and high specificity are important for different reasons. By definition, an undifferentiated neoplasm lacks morphologic features to unequivocally substantiate sarcoma, lymphoma, carcinoma, or melanoma. Thus, antibodies with low sensitivity that fail to mark a significant percent of cases will provide inconclusive or erroneous information. The failure of an antibody to stain a particular tissue could be a true-negative (valuable information) or a false-negative (misleading information) result. Obviously, when antibodies have a sufficiently low sensitivity, their use is a liability rather than an advantage. Specificity is obviously important. When an undifferentiated neoplasm is found to be "positive" for a particular marker, there is a tendency to immediately categorize the neoplasm. In this setting, when histologic features of cellular differentiation are totally lacking, an extreme degree of trust is being placed on the immunohistochemical technique. From our earlier discussion it is apparent that perfect sensitivity and specificity do not exist among most immunohistochemical reagents. Accordingly, the safest approach is to use a panel of antibodies that will disclose anomalous immunohistochemical reactions (e.g., a neoplasm positive for both keratin and LCA). Specimens from such cases should be carefully evaluated with additional monoclonal antibodies and scrutinized by light microscopy. Furthermore, while immunohistochemistry provides for rapid and cost-effective diagnosis, electron microscopy may still contribute valuable information. Despite our best intentions and desires, it is also clear that a small percentage of "undifferentiated" neoplasms will remain undifferentiated. Quality control and quality assurance are two final, but important, issues to address. An extraordinary large number of variables in tissue selection, fixation, and processing can skew results.(ABSTRACT TRUNCATED AT 400 WORDS)
一个理想的免疫组织化学筛选组合应是其中每种抗体对目标细胞类型（如上皮性肿瘤、淋巴瘤、肉瘤等的标志物）的敏感性和特异性均为100%。任何从事过免疫化学工作的人都清楚这种情况并不存在。通过福尔马林固定和常规组织处理导致关键抗原丢失，从而阻碍了高敏感性。虽然通过处理新鲜冷冻、冻干或塑料包埋的标本可提高敏感性，但病理学家通常认为这些方法不方便。特异性是一个更隐蔽的问题。随着单克隆抗体技术的出现，许多人将单特异性（如标记一种抗原决定簇）等同于组织特异性。当然并非如此，因为一种单克隆抗体识别的决定簇可能在不同谱系的细胞上表达。高敏感性和高特异性因其不同原因而重要。根据定义，未分化肿瘤缺乏明确证实为肉瘤、淋巴瘤、癌或黑色素瘤的形态学特征。因此，敏感性低且未能标记相当比例病例的抗体将提供不确定或错误的信息。抗体未能对特定组织染色可能是真阴性（有价值的信息）或假阴性（误导性信息）结果。显然，当抗体敏感性足够低时，使用它们是一种负担而非优势。特异性显然很重要。当发现未分化肿瘤对特定标志物呈“阳性”时，往往会立即对肿瘤进行分类。在这种情况下，当完全缺乏细胞分化的组织学特征时，就过度依赖免疫组织化学技术了。从我们前面的讨论中可以明显看出，大多数免疫组织化学试剂并不存在完美的敏感性和特异性。因此，最安全的方法是使用一组抗体，以揭示异常的免疫组织化学反应（如肿瘤对角蛋白和LCA均呈阳性）。对此类病例的标本应使用额外的单克隆抗体进行仔细评估，并通过光学显微镜进行检查。此外，虽然免疫组织化学可实现快速且经济高效的诊断，但电子显微镜仍可能提供有价值的信息。尽管我们有良好的意愿和期望，但很明显仍有一小部分“未分化”肿瘤将保持未分化状态。质量控制和质量保证是最后但重要的两个问题。组织选择、固定和处理中存在大量变量可能会使结果产生偏差。（摘要截取自400字）
