PDF(Pubmed)
Abstract：
BACKGROUND: Liposarcomas are among the most common mesenchymal malignancies. However, the therapeutic options are still very limited and so far, targeted therapies had not yet been established. Immunotherapy, which has been a breakthrough in other oncological entities, seems to have no efficacy in liposarcoma. Complicating matters further, classification remains difficult due to the diversity of morphologies and nonspecific or absent markers in immunohistochemistry, leaving molecular pathology using FISH or sequencing as best options. Many liposarcomas harbor MDM2 gene amplifications. In close relation to the gene locus of MDM2, HER3 (ERBB3) gene is present and co-amplification could occur. Since the group of HER/EGFR receptor tyrosine kinases and its inhibitors/antibodies play a role in a broad spectrum of oncological diseases and treatments, and some HER3 inhibitors/antibodies are already under clinical investigation, we hypothesized that in case of HER3 co-amplifications a tumor might bear a further potential therapeutic target.
METHODS: We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma.
RESULTS: Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy.
CONCLUSIONS: Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.
METHODS: We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma.
RESULTS: Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy.
CONCLUSIONS: Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.
摘要：
背景：脂肪肉瘤是最常见的间充质恶性肿瘤之一。然而,治疗选择仍然非常有限，到目前为止，靶向治疗尚未建立.免疫疗法,这是其他肿瘤实体的突破，似乎对脂肪肉瘤没有疗效。使事情进一步复杂化，分类仍然是困难的，由于形态学的多样性和非特异性或缺乏在免疫组织化学标记，使用FISH或测序作为最佳选择的分子病理学。许多脂肪肉瘤携带MDM2基因扩增。与MDM2的基因座密切相关，存在HER3（ERBB3）基因，并且可以发生共扩增。由于HER/EGFR受体酪氨酸激酶及其抑制剂/抗体在广泛的肿瘤疾病和治疗中起作用，一些HER3抑制剂/抗体已经在临床研究中，我们假设在HER3共扩增的情况下,肿瘤可能具有进一步的潜在治疗靶点.
方法：我们对56例存档病例进行了FISH分析（MDM2、DDIT3、HER3），随后进行了重新分类以确认脂肪肉瘤的诊断。
结果：在56例病例中，有16例需要重新分类，在54个案例中，有20个，可以检测到HER3的簇扩增，与MDM2扩增显着相关。我们的研究表明，脂肪肉瘤的实体显示出特定的分子特征，导致现代，既定的方法论。此外,在57.1%的病例中，HER3被大量簇扩增，为靶向治疗提供了一个推定的治疗靶点。
结论：我们的研究为进一步研究HER3基因作为脂肪肉瘤的假定治疗靶点奠定了基础。
方法：我们对56例存档病例进行了FISH分析（MDM2、DDIT3、HER3），随后进行了重新分类以确认脂肪肉瘤的诊断。
结果：在56例病例中，有16例需要重新分类，在54个案例中，有20个，可以检测到HER3的簇扩增，与MDM2扩增显着相关。我们的研究表明，脂肪肉瘤的实体显示出特定的分子特征，导致现代，既定的方法论。此外,在57.1%的病例中，HER3被大量簇扩增，为靶向治疗提供了一个推定的治疗靶点。
结论：我们的研究为进一步研究HER3基因作为脂肪肉瘤的假定治疗靶点奠定了基础。
