Laboratory of Solid Tumor Genetics, University Hospital of Nice-Côte d'Azur University, Nice, France; Laboratory of Solid Tumor Genetics, Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR 7284/INSERM U1081, Nice, France.
Department of Cancer Biology, Paoli-Calmettes Institute, Marseille, France.
Neoplasia. 2020 Aug;22(8):311-321. doi: 10.1016/j.neo.2020.05.003. Epub 2020 Jun 16.
The detection of specific alterations by genetic analyses has been included in the diagnostic criterions of the World Health Organization's classification of soft tissues tumors since 2013. The presence of a SS18 rearrangement is pathognomonic of synovial sarcoma (SS). MDM2 amplification is strongly correlated to well-differentiated or dedifferentiated liposarcoma (DDLPS) in the context of sarcoma. We identified one case of poorly differentiated sarcoma harboring both SS18-SSX2 fusion and MDM2 amplification. The review of the literature showed high discrepancies, concerning the incidence of MDM2 amplification in SS: from 1.4% up to 40%. Our goal was to precisely determine the specific clinico-pathological features of this case and to estimate the frequency and characteristics of the association of SS18-SSX fusion/MDM2 amplification in sarcomas. We performed a retrospective and prospective study in 96 sarcomas, (56 SS and 40 DDLPS), using FISH and/or array-CGH to detect MDM2 amplification and SS18 rearrangement. None of the 96 cases presented both genetic alterations. Among the SS, only the index case (1/57: 1.7 %) presented the double anomaly. We concluded that MDM2 amplification in SS is a very rare event. The final diagnosis of the index case was a SS with SS18-SSX2 and MDM2 amplification as a secondary alteration. If the detection of MDM2 amplification is performed first in a poorly differentiated sarcoma, that may lead to not search other anomalies such as SS18 rearrangement and therefore to an erroneous diagnosis. This observation emphasizes the strong complementarity between histomorphology, immunohistochemistry and molecular studies in sarcoma diagnosis.
自 2013 年以来，通过基因分析检测特定改变已被纳入世界卫生组织软组织肿瘤分类的诊断标准。SS18 重排的存在是滑膜肉瘤（SS）的特征性表现。MDM2 扩增与分化良好或去分化脂肪肉瘤（DDLPS）在肉瘤中密切相关。我们鉴定了一例同时具有 SS18-SSX2 融合和 MDM2 扩增的低分化肉瘤。文献复习显示，MDM2 扩增在 SS 中的发生率存在很大差异：从 1.4%到 40%不等。我们的目标是准确确定该病例的具体临床病理特征，并估计 SS18-SSX 融合/MDM2 扩增在肉瘤中的频率和特征。我们对 96 例肉瘤（56 例 SS 和 40 例 DDLPS）进行了回顾性和前瞻性研究，使用 FISH 和/或 array-CGH 检测 MDM2 扩增和 SS18 重排。96 例病例均未同时存在这两种遗传改变。在 SS 中，仅索引病例（57 例中的 1 例：1.7%）存在双重异常。我们得出结论，MDM2 扩增在 SS 中是一种非常罕见的事件。索引病例的最终诊断为 SS，具有 SS18-SSX2 和 MDM2 扩增作为次要改变。如果在低分化肉瘤中首先检测到 MDM2 扩增，可能会导致不寻找其他异常，如 SS18 重排，从而导致错误的诊断。这一观察结果强调了组织形态学、免疫组织化学和分子研究在肉瘤诊断中的强互补性。
