目的:去分化脂肪肉瘤(DDLPS)的特征是非脂肪源性肉瘤区与富含脂肪细胞的高分化区域共存。12q13-15区域的扩增包括MDM2和DDIT3基因。MDM2扩增被认为是DDLPS的遗传标志,而DDIT3通常在粘液样脂肪肉瘤中重排。最近的研究表明,DDLPS中DDIT3的扩增与粘液样脂肪肉瘤(LPS样)形态有关。我们的研究旨在通过FISH评估DDLPS中MDM2和DDIT3的状态,并将其与MLPS样特征相关联。
方法:对6例MLPS样形态DDLPS患者进行病理调查,免疫组织化学,和基因。建立具有经典DDLPS形态和高分化脂肪肉瘤(WDLPS)的对照组,并进行分子评估。进行常规诊断中使用的荧光原位杂交(FISH)以确定MDM2和DDIT3基因的状态。
结果:患者的平均年龄为64岁(43至85岁),男女比例为5:4。肿瘤位于腹膜后(15)和腹膜后(3)。所有病例均显示包含MDM2基因的12q15区域的扩增和代表DDIT3端粒标签的5'DDIT3FISH探针的共扩增。然而,我们没有发现之前报道的黏液样LPS形态与DDIT3扩增的关系.
结论:来自具有黏液样区域的DDLPS的活检材料可被错误分类为黏液样脂肪肉瘤。的确,根据组织学图像,可以首先评估DDIT3状态。在这些情况下,我们显示通过FISH评估的DDIT3端粒标签扩增,是一种常见的,非特定特征,在经典DDLPS和WDLPS中也可以找到。因此,我们认为,由于FISH方法的规范,DDIT3和MDM2的共扩增可能被认为是12q13-15区域扩增的频谱。
OBJECTIVE: Dedifferentiated liposarcoma (DDLPS) is characterized by non-lipogenic sarcoma fields coexisting with adipocyte-rich well-differentiated areas. Amplification of the 12q13-15 region includes the MDM2 and DDIT3 genes. MDM2 amplification is considered a genetic hallmark of DDLPS, while DDIT3 is typically rearranged in myxoid liposarcoma. Recent studies showed that DDIT3 amplification is associated with myxoid liposarcoma-like (LPS-like) morphology in DDLPS. Our study aimed to evaluate the status of MDM2 and DDIT3 by FISH in DDLPS and correlate it with MLPS-like features.
METHODS: Six patients with MLPS-like morphology DDLPS were investigated pathologically, immunohistochemically, and genetically. The control groups of patients with classical DDLPS morphology and well-differentiated liposarcoma (WDLPS) were established and molecularly assessed as well. Fluorescence in situ hybridization (FISH) used in routine diagnostics was performed to determine the status of MDM2 and DDIT3 genes.
RESULTS: The patient\'s mean age was 64 (range from 43 to 85 years) with a 5:4 male to female ratio. Tumors were localized retroperitoneally (15) and extra-retroperitoneally (3). All cases demonstrated amplification of the 12q15 region containing MDM2 gene and co-amplification of the 5\' DDIT3 FISH Probe representing DDIT3 telomeric tag. However, we did not find the relation of myxoid LPS-like morphology with DDIT3 amplification as previously reported.
CONCLUSIONS: The biopsy material from DDLPS with myxoid areas can be misclassified as myxoid liposarcoma. Indeed, according to the histological image, DDIT3 status may be evaluated first. In these cases, we show that the DDIT3 telomeric tag amplification assessed by FISH, is a common, nonspecific feature, which is also found in classical DDLPS and WDLPS. Therefore, we believe that co-amplification of DDIT3 and MDM2 may be considered a spectrum of the 12q13-15 region amplification due to the specification of FISH methodology.