The clinical implication of SS18-SSX fusion gene in synovial sarcoma

Background:

The aim of this study is to evaluate distribution and clinical impact of the SS18-SSX fusion gene in patients with synovial sarcoma in China.

Methods:

We collected and analysed the clinical data of 88 patients using univariate and multivariate survival analysis. HEK 293T and NIH 3T3 cell lines were transfected with the SS18-SSX1 or SS18-SSX2 gene to determine the respective involvement of these fusion genes in cell proliferation and invasion.

Results:

Overall survival was significantly better among SS18-SSX2 cases (P=0.001), FNCLCC grade 2 cases (P<0.001), and UICC stage 1 or 2 (P<0.001) by univariate and multivariate survival analysis. SS18-SSX1-positive cells were more proliferative and invasive than SS18-SSX2-positive cells.

Conclusion:

SS18-SSX fusion type is a significant prognostic factor for patients with synovial sarcoma.     

腹膜后滑膜肉瘤6例临床病理及分子病理学分析

目的:探讨腹膜后滑膜肉瘤的临床病理特征、免疫表型及分子遗传学改变。方法:收集北京大学国际医院病理科2014年12月至2021年07月期间手术切除腹膜后标本病理诊断为滑膜肉瘤6例,进行光镜观察、免疫表型及分子病理学分析,并复习相关文献。结果:男性2例,女性4例,年龄12~56岁（平均年龄29岁,中位年龄26岁）;肿瘤大小8~20 cm,平均15.2 cm,界限较清,梭形细胞型5例,双相型1例;CKpan、EMA、Bcl-2、CD99、TLE1、Vimentin、CD34、Calponin阳性比例分别为5/6、6/6、6/6、3/6、6/6、5/6、0/6、4/6,INI1呈特殊模式表达6/6,Ki-67高表达;FISH结果显示6例均有SS18-SSX基因融合;3例为SS18-SSX2基因融合,并有伴随基因突变。结论:腹膜后滑膜肉瘤是少见的发病部位,明确诊断常需结合组织病理学形态、免疫组织化学表达及分子遗传学特征进行综合分析。     

滑膜肉瘤相关发病机制的研究进展

滑膜肉瘤（synovial sarcoma, SS）是源于关节、滑膜及腱鞘滑膜的软组织恶性肿瘤,因其在关节周围的经典表现而得名。滑膜肉瘤可发生在身体任何部位,但以四肢近关节处多见。95%的SS以t（X;18）（p11.2-q11.2）染色体易位为特点,形成融合基因SYT-SSX,从而通过Wnt/β-catenin、PcG和ERK等信号通路促进SS细胞发生。另外,TGF-β1、Smad、Snail和Slug通过EMT途径也参与SS的发生发展。除此之外SS的发病还涉及有许多因子改变,如Twist1、Bmi1等。近年来研究表明上述因素均和SS的发病机制有关。本文将对这些因素在SS发生发展方面的作用作一概述。     

Twist 和Snail 在滑膜肉瘤中的表达*

目的:检测上皮- 间充质转换的转录因子Twist和Snail在滑膜肉瘤组织中的表达,分析二者之间关系及其对滑膜肉瘤远处转移的影响,并探讨其预后意义。方法:通过组织病理学观察和免疫组织化学染色,检测133 例滑膜肉瘤组织标本中Twist和Snail的表达情况,应用统计学软件SPSS13.0 分析二者的不同表达与各临床病理参数特点的关系,并作Kaplan Meier生存分析。结果:Twist和Snail在滑膜肉瘤组织中表达部位为细胞质和/或细胞核,133 例组织标本中Twist高表达者55例（55/133）且与组织学分型、临床分期以及融合基因类型有关（P<0.05）;Snail高表达者82例（82/133）,与组织学分型有关（P<0.05）。 二者的表达与不同性别、年龄、肿瘤大小、部位、组织学分级等无关（P>0.05）。 Twist和Snail在滑膜肉瘤组织中的表达存在正相关（r s=0.191,P=0.027）,Log-Rank test 显示Twist高表达组,患者总生存期和无转移生存期明显低于低表达组,差异有统计学意义（χ2=8.620,P=0.03和χ2=11.462,P=0.001）;Snail高表达组,患者无转移生存期明显低于其弱表达者,差异有统计学意义（χ2=4.575,P=0.032）,但两组的总生存期差异无统计学意义（χ2=0.602,P=0.438）;且二者联合表达组患者总生存期和无转移生存期明显低于其弱表达组,差异有统计学意义（χ2=13.619,P=0.003 和χ2=15.548,P=0.001）。 结论:滑膜肉瘤组织中存在EMT 的主要转录因子Twist和Snail的高表达,二者可独立诱导EMT ,且二者的联合表达更加促进肿瘤转移的发生,提示患者预后不良。      

Genome-wide analysis of gene expression in synovial sarcomas using a cDNA microarray

Among a histologically heterogeneous group of soft tissue sarcomas, synovial sarcoma (SS) is regarded as a "miscellaneous" entity of uncertain origin. Although recent molecular analysis has disclosed involvement of a specific chromosomal translocation in the pathogenesis of SS, its genetic features remain largely unclear. In the work reported here we examined genome-wide gene expression profiles of 13 SS cases and 34 other spindle-cell sarcoma cases by cDNA microarray consisting of 23,040 genes. A hierarchical clustering analysis grouped SS and malignant peripheral nerve sheath tumor into the same category, and these two types of tumor shared expression patterns of numerous genes relating to neural differentiation. Several genes were up-regulated in almost all SS cases, and the presumed functions of known genes among them were related to migration or differentiation of neural crest cells, suggesting the possibility of neuroectodermal origin of SS. Moreover, we identified a set of genes that divided SS cases into two putative subclasses, a feature that may shed light on novel biological aspects of SS in addition to those having to do with epithelial differentiation. These data have provided clues for understanding the origin and tumorigenesis of SS.     

Establishment and characterization of malignant rhabdoid tumor of the kidney

Malignant rhabdoid tumor of the kidney (MRTK) is a highly aggressive tumor which occurs in childhood and which is histologically characterized by the existence of eosinophilic intracytoplasmic inclusions. We established and characterized a cell line from this tumor with histological, immunohistochemical and cytogenetical analysis. Histologically, the tumor cells demonstrate typical eosinophilic inclusions, while immunohistochemically the cells demonstrate common mesenchymal and epithelial differentiation. Although the conventional karyotyping of this tumor lacked the abnormalities of 22q chromosome, Southern blot analysis and microsatellite analysis verified abnormalities of the BCR gene and of the hSNF5/INI1 gene. Despite the variety of locations, these common genetic abnormalities appear to contribute to distinguish rhabdoid tumor from such other small round cell tumors as primitive neuroectodermal tumor, rhabdomyosarcoma, poorly differentiated synovial sarcoma and desmoplastic small round cell tumor.     

Twist 对EMT 调控在循环肿瘤细胞监测与抗癌药物评价中的临床意义*

肿瘤细胞的上皮间质可塑性变化包括上皮- 间质化（epithelial-mesenchymal transition ,EMT ）和间质- 上皮转化（mesenchymal-epithelial transition,MET ）的可逆过程,在循环肿瘤细胞（circulating tumor cells ,CTCs）形成、转归及肿瘤转移过程中起到重要作用。Twist在人横纹肌肉瘤、乳腺癌、胃癌等多种肿瘤中过表达,肿瘤细胞中Twist与多种信号通路连接,形成复杂的网状环路参与调控CTCs中EMT/MET的发生并促进肿瘤细胞向远处转移。因此,通过监测CTCs中Twist本身以及所调控的上皮- 间质表型分子标志物的变化,不仅可以增加肿瘤标志物CTCs的检出率,提供肿瘤临床分期及预后评估的直接证据;而且,对于评估多种抗肿瘤药物的疗效及耐药机制均具有重要的临床意义。