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MDM2 和 CDK4 能否诊断高分化/去分化脂肪肉瘤?129 例软组织肿瘤的免疫组化研究。

Can MDM2 and CDK4 make the diagnosis of well differentiated/dedifferentiated liposarcoma? An immunohistochemical study on 129 soft tissue tumours.

机构信息

Center For Research and Post-graduation Heitor Cirne Lima, Universidade Federal de Ciências da Saúde de Porto Alegre, 90050-170, Porto Alegre, Rio Grande do Sul, Brazil.

出版信息

J Clin Pathol. 2009 Dec;62(12):1127-35. doi: 10.1136/jcp.2009.070201.

DOI:10.1136/jcp.2009.070201
PMID:19946100
Abstract

BACKGROUND

Well differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) have been shown to have supernumerary chromosomes with amplified sequences of the MDM2 and CDK4 genes. MDM2 and CDK4 protein overexpression have also been identified in these tumours.

AIM

To investigate whether immunohistochemistry (IHC) for MDM2 and CDK4 can be used to diagnose WDLPS and DDLPS.

METHODS

IHC for MDM2/CDK4 was carried out on a series of 129 paraffin-embedded lipomatous and non-lipomatous soft tissue tumours. The cases were divided into four groups: WDLPS (n = 19), DDLPS (n = 10), benign adipocytic tumours (BAT) (n = 17), and other mesenquimal tumours (OMT) (n = 83). IHC results were compared in each group and the diagnostic efficacy of the test in identifying WDLPS and DDLPS among the other soft tissue tumours was determined. A percentage of tumour cell positivity was evaluated to better characterise the pattern of tumour immunostaining.

RESULTS

Sensitivity and specificity of positive MDM2 and CDK4 immunostainings to identify WDLPS among BAT was 100% and 58.8%, and 68.4% and 88.2%, respectively. When distinguishing DDLPS from OMT, sensitivity and specificity of MDM2 and CDK4 were 90% and 65%, and 70% and 96.3%, respectively. The highest specificity was achieved when a case was considered positive with strong and diffuse immunoreactivity in more than 30% of the neoplastic cells (94.1% and 100%, and 77.1% and 98.8%, respectively).

CONCLUSION

Detection of MDM2/CDK4 protein overexpression by IHC can be used by pathologists to diagnose WDLPS and DDLPS. Considering a strong and diffuse immunostaining pattern in most of the neoplastic cells achieves the best results in identifying these tumours.

摘要

背景

高分化脂肪肉瘤(WDLPS)和去分化脂肪肉瘤(DDLPS)已被证实存在超数染色体,其 MDM2 和 CDK4 基因序列扩增。这些肿瘤中也存在 MDM2 和 CDK4 蛋白的过表达。

目的

研究免疫组化(IHC)检测 MDM2 和 CDK4 是否可用于诊断 WDLPS 和 DDLPS。

方法

对 129 例石蜡包埋的脂肪性和非脂肪性软组织肿瘤进行了 MDM2/CDK4 的免疫组化检测。将病例分为四组:WDLPS(n=19)、DDLPS(n=10)、良性脂肪性肿瘤(BAT)(n=17)和其他间叶性肿瘤(OMT)(n=83)。比较了每组的免疫组化结果,并确定了该检测方法在识别其他软组织肿瘤中的 WDLPS 和 DDLPS 的诊断效果。评估了肿瘤细胞阳性百分比,以更好地描述肿瘤免疫染色的模式。

结果

在 BAT 中,MDM2 和 CDK4 免疫染色阳性对诊断 WDLPS 的敏感性和特异性分别为 100%和 58.8%,68.4%和 88.2%。在区分 DDLPS 和 OMT 时,MDM2 和 CDK4 的敏感性和特异性分别为 90%和 65%,70%和 96.3%。当将病例定义为强阳性且超过 30%的肿瘤细胞弥漫性免疫反应时,特异性最高(分别为 94.1%和 100%,77.1%和 98.8%)。

结论

免疫组化检测 MDM2/CDK4 蛋白过表达可用于病理学家诊断 WDLPS 和 DDLPS。考虑到大多数肿瘤细胞中存在强而弥漫的免疫染色模式,可在鉴定这些肿瘤时获得最佳结果。

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