Diagnostic use of fluorescence in situ hybridization in expert review in a phase 2 study of trabectedin monotherapy in patients with advanced, translocation-related sarcoma.
Diagnostic use of fluorescence in situ hybridization in expert review in a phase 2 study of trabectedin monotherapy in patients with advanced, translocation-related sarcoma.
复制标题
DOI：
10.1186/s13000-016-0486-2
复制
发表时间：
2016-04-12
影响因子：
2.6
通讯作者：
Hasegawa T
中科院分区：
文献类型：
--
作者：
Sugita S;Asanuma H;Hasegawa T
荧光原位杂交（FISH）是病理诊断中最强大的遗传分析工具之一。FISH可以检测各种遗传异常，包括易位相关肉瘤（TRSs）中特异性发现的基因易位。在此，我们报告了在trabectedin单药治疗晚期TRS患者的2期研究中使用FISH进行专家评审。TRS患者（n = 76）在12个研究地点进行病理诊断，包括通过基因检测进行有或无易位证据的形态学检查后，纳入试验。在对研究地点的代表性标本进行组织学检查后，我们使用适当的抗体和FISH进行免疫组织化学，以在专家审查中对肿瘤类型进行遗传确认。在76例TRS病例中，在研究部位诊断的3例滑膜肉瘤中，FISH未检测到SS18探针的分裂信号。恶性周围神经鞘瘤2例，肉瘤样癌1例。其中一例为小圆细胞型MPNST。排除这3例后，我们评估了另外73例。在73例患者中，有7例由于脱钙和过度固定手术，FISH分析未检测到分裂信号。排除这7例，FISH在95%（63/66）的研究病例中检测到易位，灵敏度很高。FISH对TRS的诊断具有很高的敏感性，可以对病理诊断进行遗传确认。我们强烈推荐FISH作为TRS的确证性诊断试验，这将有助于选择trabectedin预期有效的TRS患者。本研究部分已在日本医药信息中心注册，编号为JapicCTI-121850。
Fluorescence in situ hybridization (FISH) is one of the most powerful genetic analysis tools for pathological diagnoses. FISH can detect various genetic abnormalities including gene translocation that was specifically found in translocation-related sarcomas (TRSs). Here, we report the use of FISH in expert review in a phase 2 study of trabectedin monotherapy for patients with advanced TRS. TRS patients (n = 76) were enrolled in the trial at 12 study sites after pathological diagnoses were made, including morphological examination with or without evidence of translocation by genetic testing. Following histological reviews of the representative specimens at the study sites, we performed immunohistochemistry using the appropriate antibodies and FISH for genetic confirmation of the tumor types in the expert review. Among the 76 TRS cases, no split signal for SS18 probe was detected by FISH in three synovial sarcoma cases that were diagnosed at the study sites. Malignant peripheral nerve sheath tumor (MPNST) was diagnosed in two cases and sarcomatoid carcinoma in one. One of the cases was a small round cell variant of MPNST. After excluding these three cases, we assessed the other 73. There were no split signals detected in 7 of the 73 cases by FISH analysis, due to decalcification and hyperfixation procedures. Excluding these seven cases, FISH detected translocations in 95 % (63/66) of the study cases with a high sensitivity. The diagnosis of TRS by FISH was highly sensitive and enabled genetic confirmation of the pathological diagnoses. We strongly recommend FISH as a confirmatory diagnostic test for TRS, which would enable the selection of patients with TRS in whom trabectedin is expected to be effective. This study was done in part that registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.