Anderson William J, Jo Vickie Y
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Diagnostics (Basel). 2021 Apr 12;11(4):690. doi: 10.3390/diagnostics11040690.
The diagnosis of benign and malignant soft tissue and bone neoplasms is a challenging area of surgical pathology, due to the large number, rarity, and histologic diversity of tumor types. In recent years, diagnosis and classification has been aided substantially by our growing understanding of recurrent molecular alterations in these neoplasms. Concurrently, the role of diagnostic immunohistochemistry has also expanded, with the development of numerous biomarkers based on underlying molecular events. Such biomarkers allow us to infer the presence of these events and can therefore substitute for other ancillary molecular genetic techniques (e.g., fluorescence in situ hybridization, polymerase chain reaction, and next-generation sequencing). In this review, we discuss a range of biomarkers currently available for these neoplasms, highlighting the accuracy, staining characteristics, and interpretation pitfalls of each antibody. These include immunohistochemical antibodies that represent reliable surrogates for the detection of gene fusions (e.g., STAT6, CAMTA1, FOSB, DDIT3) and more recently described breakpoint-specific antibodies (e.g., SS18-SSX, PAX3/7-FOXO1). Additionally, discussed are markers that correlate with the presence of gene amplifications (e.g., MDM2, CDK4), deletions (e.g., SMARCB1, SMARCA4), single nucleotide variants (e.g., G34W, K36M), aberrant methylation (H3K27me3), and increased expression as discovered through gene expression profiling (e.g., MUC4, DOG1, ETV4, NKX2.2, NKX3.1).
良性和恶性软组织及骨肿瘤的诊断是外科病理学中一个具有挑战性的领域，这是因为肿瘤类型数量众多、较为罕见且组织学表现多样。近年来，随着我们对这些肿瘤中反复出现的分子改变的认识不断加深，诊断和分类得到了极大的帮助。与此同时，随着基于潜在分子事件的众多生物标志物的开发，诊断性免疫组织化学的作用也得到了扩展。此类生物标志物使我们能够推断这些事件的存在，因此可以替代其他辅助分子遗传学技术（例如，荧光原位杂交、聚合酶链反应和下一代测序）。在本综述中，我们讨论了目前可用于这些肿瘤的一系列生物标志物，重点介绍了每种抗体的准确性、染色特征和解读陷阱。这些包括代表检测基因融合可靠替代物的免疫组织化学抗体（例如，STAT6、CAMTA1、FOSB、DDIT3）以及最近描述的断点特异性抗体（例如，SS18 - SSX、PAX3/7 - FOXO1）。此外，还讨论了与基因扩增（例如，MDM2、CDK4）、缺失（例如，SMARCB1、SMARCA4）、单核苷酸变异（例如，G34W、K36M）、异常甲基化（H3K27me3）以及通过基因表达谱发现的表达增加（例如，MUC4、DOG1、ETV4、NKX2.2、NKX3.1）相关的标志物。
