Sugita Shintaro, Hasegawa Tadashi
Department of Surgical Pathology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
J Orthop Sci. 2017 Jul;22(4):601-612. doi: 10.1016/j.jos.2017.02.004. Epub 2017 Mar 6.
During routine pathological examination, fluorescence in situ hybridization (FISH) plays a significant role in the genetic analysis of samples. FISH can detect genetic abnormalities such as chromosomal translocations, gene amplifications, and deletions in formalin-fixed, paraffin-embedded (FFPE) specimens. Due to its practical advantages, FISH is already used in many pathology laboratories. It is especially useful for the diagnosis of translocation-related sarcomas (TRSs), which comprise about 25% of soft tissue sarcomas. Because TRSs have specific chimeric genes derived from characteristic chromosomal translocations, their diagnosis would not be possible without FISH. FISH significantly contributes to the genetic confirmation of TRS. Analysis using next-generation sequencing (NGS), the latest powerful method for comprehensive genomic analysis, has recently revealed many kinds of chromosomal translocations in various TRSs. We often use experimental results to create custom probes for FISH and have applied NOCA2 split probes and CIC split, CIC-FOXO4 fusion probes to the pathological diagnosis of soft tissue angiofibroma and CIC-rearranged sarcoma, respectively. Some chimeric fusions detected by NGS induce the expression of related proteins and their detection using immunohistochemistry is beneficial for pathological diagnosis. We previously identified characteristic FOSB expression in pseudomyogenic hemangioendothelioma (PHE) with a specific SERPINE1-FOSB fusion, revealing the usefulness of FOSB immunohistochemistry in the differential diagnosis of PHE and its mimics. Finally, we participated in a central review of a clinical trial of trabectedin monotherapy. We guaranteed an accurate diagnosis by using FISH and genetic confirmation to select appropriate TRS patients and thereby confirm the accuracy of the patient enrollment of the clinical trial. FISH is an essential tool for the pathological diagnosis of soft tissue and bone tumors. It can detect various genetic abnormalities in an "in situ" fashion using FFPE specimens on glass slides during routine examination. It is also an excellent tool for translating the latest experimental findings to practical use in routine pathological diagnosis. Further instrumental improvements in FISH will help it to become the universal method for the genetic analysis of pathological diagnoses.
在常规病理检查中，荧光原位杂交（FISH）在样本的基因分析中发挥着重要作用。FISH能够检测福尔马林固定、石蜡包埋（FFPE）标本中的基因异常，如染色体易位、基因扩增和缺失。由于其实际优势，FISH已在许多病理实验室中得到应用。它对于诊断与易位相关的肉瘤（TRS）特别有用，这类肉瘤约占软组织肉瘤的25%。由于TRS具有源自特征性染色体易位的特定嵌合基因，没有FISH就无法进行诊断。FISH对TRS的基因确认有显著贡献。使用新一代测序（NGS）进行分析，这是目前用于全面基因组分析的强大最新方法，最近在各种TRS中发现了多种染色体易位。我们经常利用实验结果为FISH创建定制探针，并分别将NOCA2分裂探针和CIC分裂、CIC-FOXO4融合探针应用于软组织血管纤维瘤和CIC重排肉瘤的病理诊断。通过NGS检测到的一些嵌合融合会诱导相关蛋白的表达，使用免疫组织化学检测这些蛋白对病理诊断有益。我们之前在具有特定SERPINE1-FOSB融合的假肌源性血管内皮瘤（PHE）中鉴定出特征性的FOSB表达，揭示了FOSB免疫组织化学在PHE及其相似病变鉴别诊断中的有用性。最后，我们参与了曲贝替定单药治疗临床试验的中心审查。我们通过使用FISH和基因确认来保证准确诊断，以选择合适的TRS患者，从而确认临床试验患者入组的准确性。FISH是软组织和骨肿瘤病理诊断的重要工具。它可以在常规检查期间，使用载玻片上的FFPE标本以“原位”方式检测各种基因异常。它也是将最新实验结果转化为常规病理诊断实际应用的优秀工具。FISH的进一步技术改进将有助于它成为病理诊断基因分析的通用方法。
