Diagnostic Utility of p16, CDK4, and MDM2 as an Immunohistochemical Panel in Distinguishing Well-differentiated and Dedifferentiated Liposarcomas From Other Adipocytic Tumors
Diagnostic Utility of p16, CDK4, and MDM2 as an Immunohistochemical Panel in Distinguishing Well-differentiated and Dedifferentiated Liposarcomas From Other Adipocytic Tumors
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DOI：
10.1097/pas.0b013e3182417330
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发表时间：
2012-03-01
影响因子：
5.6
通讯作者：
Fisher, Cyril
中科院分区：
文献类型：
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作者：
Thway, Khin;Flora, Rashpal;Fisher, Cyril
脂肪细胞肿瘤是最常见的软组织肿瘤类型。区分非典型脂肪瘤性肿瘤高分化脂肪肉瘤 (WDL) 与良性脂肪细胞肿瘤以及去分化脂肪肉瘤 (D DL) 与多形性或粘液样脂肪肉瘤 (LPS) 可能很困难。 WDL 和 DDL 的特征是 MDM2 和 CDK4 细胞周期癌基因扩增，并伴有蛋白质过度表达，并且还可以过度表达细胞周期调节因子 p16。我们评估了 CDK4、MDM2 和 p16 免疫组织化学在其他脂肪细胞肿瘤 WDL/DDL 常规组织病理学诊断中的效用。对 216 例脂肪细胞肿瘤（31 例 WDL、57 例 DDL、11 例粘液样 LPS、2 例多形性 LPS、91 例脂肪瘤（包括肌内、纤维、血管和骨化亚型）、18 例梭形/多形性脂肪瘤和 6 例冬眠瘤进行了三种标记物的免疫组织化学分析。 WDLs和72%的DDLs表达全部3种抗原，而100%的WDLs和93%的DDLs表达至少2种抗原。三者检测WDLs/DDLs的敏感性和特异性分别为71%和98%，CDK4检测WDLs/DDLs的敏感性和特异性为86%和89%，MDM2的敏感性和特异性为86%和89%。 CDK4、MDM2 和 p16 的免疫组织化学三重奏分别为 74% 和 92%，是一种有用的辅助诊断工具，为区分 WDL 和 DDL 与其他脂肪细胞肿瘤提供了强有力的支持，并且可能比之前评估的 CDK4 和 MDM2 组合更敏感，p16 是检测 WDL/DDL 的最敏感和特异的标记物。 CDK4 和 p16 比两者与 MDM2 的组合更具区分价值，MDM2 是 3 个标记中敏感性和特异性最低的。
Adipocytic tumors are the most common type of soft tissue neoplasms. Distinguishing atypical lipomatous tumor-well-differentiated liposarcoma (WDL) from benign adipocytic neoplasms and dedifferentiated liposarcoma (D DL) from pleomorphic or myxoid liposarcoma (LPS) can be difficult. WDL and DDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes with protein overexpression and can also overexpress the cell cycle regulator p16. We assessed the utility of immunohistochemistry for CDK4, MDM2, and p16 in the routine histopathologic diagnosis of WDL/DDL from other adipocytic tumors. lmmunohistochemistry for the trio of markers was performed on 216 adipocytic neoplasms (31 WDLs, 57 DDLs, 11 myxoid LPS, 2 pleomorphic LPS, 91 lipomas (including intramuscular, fibro, angio, and ossifying subtypes), 18 spindle/pleomorphic lipomas, and 6 hibernomas. Sixty-eight percent of WDLs and 72% of DDLs expressed all 3 antigens, whereas 100% of WDLs and 93% of DDLs expressed at least 2 antigens. The sensitivity and specificity of the trio for detecting WDLs/DDLs were 71% and 98%, respectively. The sensitivity and specificity of CDK4 for detecting WDLs/DDLs were 86% and 89%, those of MDM2 were 86% and 74%, and those of p16 were 93% and 92%, respectively. The immunohistochemical trio of CDK4, MDM2, and p16 is a useful ancillary diagnostic tool that provides strong support in distinguishing WDLs and DDLs from other adipocytic neoplasms and is potentially more sensitive than previously assessed combinations of CDK4 and MDM2. p16 was the most sensitive and specific marker for detecting WDL/DDL, and the combination of CDK4 and p16 is of more discriminatory value than the combination of either with MDM2, the least sensitive and specific of the 3 markers.