Institut Nationalde la Santé et de la Recherche Médicale (INSERM) U916-Institut Bergonie, France.
J Clin Oncol. 2013 Feb 10;31(5):608-15. doi: 10.1200/JCO.2012.46.0147. Epub 2013 Jan 14.
Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS.
One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach.
CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.
Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology.
滑膜肉瘤（SS）可发生于儿童和成人，但转移事件在成人中更为常见。虽然 t(X;18)易位在 SS 肿瘤发生中的重要性已得到充分证实，但 SS 转移的遗传基础仍知之甚少。我们最近报道了与染色体完整性相关的表达（CINSARC；肉瘤复杂性指数）和基因组指数预后标志在肉瘤和胃肠道间质瘤中。在此，我们研究了这些标志是否也可以预测 SS 的结局。
选择了 100 名患有原发性未治疗 SS 肿瘤的患者，采用训练/验证方法进行表达和基因组分析。
CINSARC 和基因组指数具有很强的独立验证预后价值（P<0.001）。通过比较有或无转移的肿瘤表达谱，确定了与 CINSARC 标志共同的 14 个基因，其中排名前两位的基因 KIF14 和 CDCA2 在独立队列中被验证为预后标志物。比较成人和儿童 SS 的基因组谱，我们表明转移与两种情况下的基因组复杂性密切相关，并且成人基因组更频繁地重排。因此，具有均匀基因组谱的儿科患者不会发生转移。
SS 转移的发展与染色体复杂性密切相关，CINSARC 和基因组指数是验证的独立预后因素。成人和儿童之间转移频率的差异与基因组不稳定性有关，而成人的基因组不稳定性更为频繁。基因组指数可能是最好的整体生物标志物，并且考虑到从福尔马林固定样本进行基因组分析已经在病理学中使用，因此它显然是最具临床相关性的。
