文献简介

出版社:MR Erickson-Johnson et al

作  者:Michele R Erickson-Johnson, Amber R Seys

编  号:10.1038/modpathol.2009.149

关键字:lipoma; well-differentiated liposarcoma; CPM; MDM2; FISH

年  份:2009   点击量:871

文献摘要

The discrimination between well-differentiated liposarcomas/atypical lipomatous tumors and lipomas can be diagnostically challenging at the histological level. However, cytogenetic identification of ring and giant rod chromosomes supports the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor. These abnormal chromosomes are mainly composed of amplified genomic sequences derived from chromosome 12q13-15, and contain several genes, including MDM2, CDK4 (SAS), TSPAN31, HMGA2, and others. MDM2 is consistently amplified in well-differentiated liposarcomas/atypical lipomatous tumors, and up to 25% in other sarcomas. As part of a large genomic study of lipomatous neoplasms, we initially found CPM to be consistently amplified in well-differentiated liposarcomas/atypical lipomatous tumors. To further explore this initial finding, we investigated the copy number status of MDM2 and CPM by fluorescent in situ hybridization (FISH) on a series of 138 tumors and 17 normal tissues, including 32 well-differentiated liposarcoma/atypical lipomatous tumors, 63 lipomas, 11 pleomorphic lipomas, 2 lipoblastomas, 30 other tumors and 17 normal fat samples. All 32 well-differentiated liposarcoma/atypical lipomatous tumors showed amplification of MDM2 and CPM, usually 420 copies per cell. The other tumors lacked MDM2 and/or CPM amplification. Chromogenic in situ hybridization confirmed the above results on a subset of these tumors (n¼27). These findings suggest that identification of CPM amplification could be used as an alternative diagnostic tool for the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumors. 

分化良好型脂肪肉瘤/非典型脂肪瘤性肿瘤和脂肪瘤在组织学水平上是具有挑战性的鉴别诊断。然而,根据细胞遗传学来鉴定环巨杆染色体支持分化良好型脂肪肉瘤/非典型脂肪瘤性肿瘤的诊断。这些异常染色体主要由染色体12q13-15衍生的扩增的基因组序列组成,并且包含数个基因,包括MDM2,CDK4(SAS),TSPAN31,HMGA2,以及其他。MDM2在分化良好型脂肪肉瘤/非典型脂肪瘤性肿瘤持续扩增,而在其他肉瘤高达25%。作为脂肪瘤性肿瘤大基因组研究的一部分,我们最初发现CPM在分化良好型脂肪肉瘤/非典型脂肪瘤性肿瘤中持续扩增。为了进一步探讨这一初步调查结果,我们研究MDM2和CPM的拷贝数状态,通过对一系列138例肿瘤和17例正常组织中使用荧光原位杂交(FISH) 法的荧光,包括32例分化良好型脂肪肉瘤/非典型脂肪瘤性肿瘤,63例脂肪瘤,11例多形性脂肪瘤,2例成脂细胞瘤,30例其他肿瘤和17例正常脂肪样本。所有32例分化良好型脂肪肉瘤/非典型脂肪瘤性肿瘤显示MDM2和CPM的增幅,通常每个细胞420拷贝数。其他肿瘤缺乏MDM2和/或CPM的增幅。显色原位杂交证实这些肿瘤(N =27)的一个子集的上述结果。这些结果表明,CPM扩增的鉴定可以成为分化良好型脂肪肉瘤/非典型脂肪瘤性肿瘤诊断的替代性诊断工具。