Oncogenesis and classification of mixed-type liposarcoma: a radiological, histopathological and molecular biological analysis
Oncogenesis and classification of mixed-type liposarcoma: a radiological, histopathological and molecular biological analysis
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DOI：
10.1002/ijc.25390
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发表时间：
2011-02-15
影响因子：
6.4
通讯作者：
van Coevorden, Frits
中科院分区：
文献类型：
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作者：
de Vreeze, Ronald S. A.;de Jong, Daphne;van Coevorden, Frits
脂肪肉瘤分为临床病理实体，具有独特的形态谱和相互排斥的遗传改变。因此，罕见的高分化脂肪肉瘤和粘液样脂肪肉瘤合并的病例被称为混合型脂肪肉瘤，这引起了一个概念上的问题。此外，这一特征可能对治疗选择和预后有影响。在这里，我们解剖了混合型脂肪肉瘤病例中肿瘤成分的分子关系。根据术前磁共振图像（MRI）的异质性特征，选择8例混合型脂肪肉瘤。对术前活检标本和切除标本进行分析，包括对所有成分进行分子和免疫组织化学分析。作为对照，研究了黏液样脂肪肉瘤（n = 5）、圆细胞脂肪肉瘤（n = 5）和高分化脂肪肉瘤（n = 5） MRI特征均匀且方面一致的病例。所有具有异质MRI特征的患者均表现为粘液样脂肪肉瘤和高分化脂肪肉瘤的形态组成。实时聚合酶链反应显示，在MDM2和CDK4扩增缺失（5例中为0例）的情况下，8例中有5例的两组分均融合了FUS-DDIT3。在8例患者中，有3例MDM2和/或CDK4过表达，在没有黏液样脂肪肉瘤易位的情况下，多重连接依赖探针扩增（MLPA）显示扩增。所有对照患者均表现出与其形态学特征一致的分子模式。因此，混合型脂肪肉瘤不应被视为碰撞肿瘤，而应被视为单一生物实体内形态谱的极端变体，这解释了混合型脂肪肉瘤的生物学矛盾。对于具有异质MRI特征的肿瘤，应进行包括分子支持在内的详细分类进行治疗分层。
Liposarcomas are separated into clinicopathological entities with a characteristic morphological spectrum and mutually exclusive genetic alterations. Therefore, the rare occurrence of cases with combined patterns of well-differentiated liposarcoma and myxoid liposarcoma designated as mixed-type liposarcoma pose a conceptual problem. Moreover, this feature may have consequences for treatment choice and prognosis. Here, we have dissected the molecular relation of tumor components in cases of mixed-type liposarcoma. On the basis of heterogeneous preoperative magnetic resonance image (MRI) features, eight cases of mixed-type liposarcoma were selected. Preoperative biopsy samples and resection specimens were analyzed including molecular and immunohistochemical analysis on all components. As controls, cases with homogeneous MRI features and uniform aspects of myxoid liposarcoma (n = 5), round cell liposarcoma (n = 5) and well-differentiated liposarcoma (n = 5) were studied. All patients with heterogeneous MRI features showed morphological components of myxoid liposarcoma and well-differentiated liposarcoma. Real-time polymerase chain reaction showed FUS-DDIT3 fusion in both components in five of eight cases in the absence (zero of five) of MDM2 and CDK4 amplification. In three of eight patients, MDM2 and/or CDK4 were overexpressed, and amplification was shown by multiplex ligation-dependent probe amplification (MLPA) in the absence of myxoid liposarcoma translocations. All control patients showed a molecular pattern consistent with their morphological features. Therefore, mixed-type liposarcomas should not be regarded as collision tumors, but as an extreme variant of the morphological spectrum within a single biological entity, explaining the biological contradiction of mixed-type liposarcoma. For treatment stratification, detailed classification including molecular support should be performed in tumors with heterogeneous MRI features.