Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Laboratory of Cancer Genomics and Molecular Pathology, Samsung BioResearch Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Histol Histopathol. 2014 Jan;29(1):127-38. doi: 10.14670/HH-29.127. Epub 2013 Jul 15.
The amplification of MDM2 and CDK4 is the main molecular feature of well-differentiated liposarcomas (WDLS) and dedifferentiated liposarcomas (DDLS). Although the diagnostic usefulness of this molecular characteristic in liposarcomas has been investigated, its prognostic utility of quantitative gene level has not been explored. The aim of this study was to assess the prognostic significance of level of CDK4 amplification in MDM2-amplified WDLS/DDLS. MDM2 amplification in liposarcomas was confirmed by fluorescence in situ hybridization. The copy number of MDM2 and CDK4 was further determined by quantitative PCR (qPCR) and multiplex ligation-dependent probe amplification. Among 56 MDM2-amplified liposarcomas, 30 cases were assigned as WDLS, and 26 as DDLS. When liposarcomas were classified by qPCR-determined CDK4 amplification levels, the high-CDK4 group showed significantly poorer progression free survival (P=0.001) and disease specific survival (P=0.033) than the low-CDK4 group. However, MDM2 amplification level did not show prognostic significance. In WDLS/DDLS, the level of CDK4 amplification was useful for prognosis prediction and precise stratification of patients for targeted therapy.
MDM2 和 CDK4 的扩增是高分化脂肪肉瘤(WDLS)和去分化脂肪肉瘤(DDLS)的主要分子特征。虽然已经研究了这种分子特征在脂肪肉瘤中的诊断作用,但尚未探讨其在定量基因水平上的预后价值。本研究旨在评估 CDK4 扩增水平在 MDM2 扩增的 WDLS/DDLS 中的预后意义。通过荧光原位杂交证实脂肪肉瘤中的 MDM2 扩增。进一步通过定量 PCR(qPCR)和多重连接依赖性探针扩增确定 MDM2 和 CDK4 的拷贝数。在 56 例 MDM2 扩增的脂肪肉瘤中,30 例被归类为 WDLS,26 例为 DDLS。当根据 qPCR 确定的 CDK4 扩增水平对脂肪肉瘤进行分类时,高 CDK4 组的无进展生存期(P=0.001)和疾病特异性生存期(P=0.033)明显较差。然而,MDM2 扩增水平没有显示出预后意义。在 WDLS/DDLS 中,CDK4 扩增水平可用于预测预后,并对患者进行靶向治疗的精确分层。