Epithelioid Sarcoma and Unclassified Sarcoma with Epithelioid Features: Clinicopathological Variables, Molecular Markers, and a New Experimental Model
Epithelioid Sarcoma and Unclassified Sarcoma with Epithelioid Features: Clinicopathological Variables, Molecular Markers, and a New Experimental Model
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DOI：
10.1634/theoncologist.2010-0174
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发表时间：
2011-01-01
期刊：
影响因子：
5.8
通讯作者：
Lev, Dina
中科院分区：
文献类型：
--
作者：
Sakharpe, Aniket;Lahat, Guy;Lev, Dina
背景资料。上皮样肉瘤(ES)和具有上皮样特征的未分类肉瘤(USEF)是临床和治疗上未解决的问题。我们比较了ES和USEF患者的临床行为、治疗、结果和分子标志物的表达。此外，还开发了临床前ES研究模型，以实现全面的试验性研究。建立了自1992年以来收治的ES和USEF患者(n=116)的数据库。临床注释的ES-USEF组织微阵列(TMA)用于检测肿瘤相关标志物。对新建立的人ES细胞系和商品化的ES细胞系进行了鉴定和活体实验。有局部病变的ES和USEF患者的局部复发率分别为22%和25%，淋巴结转移率分别为35%和19%，远处转移率分别为41%和53%(中位随访期分别为54个月和39个月)。5年和10年疾病特异性生存率分别为88%和43%，52%和42%(ES和USEF)。TMA免疫组织化学显示整合酶相互作用蛋白(INI)-1缺失、肿瘤抗原125和P53核表达在ES中显著高于USEF。两株细胞在体内外均能保持ES细胞的形态和生化特征，INI-1基因缺失。通过实验模型扩展对ES和USEF临床行为、标志物表达和分子决定因素的了解，有望加速ES和USEF迫切需要的有效靶向治疗的发展。肿瘤学家2011；16：512-522
Background. Epithelioid sarcoma (ES) and unclassified sarcoma with epithelioid features (USEF) are clinically and therapeutically unresolved. We compared ES and USEF patients' clinical behavior, treatment, outcome, and molecular marker expression. Furthermore, preclinical ES study models were developed to enable comprehensive benchside investigations.Patients and Methods. A database of ES and USEF patients (n = 116) treated since 1992 was created. A clinically annotated ES-USEF tissue microarray (TMA) was assayed for tumor-related markers. Newly established human and commercially available ES cell lines were characterized and tested in vivo.Results. ES and USEF patients presenting with localized disease exhibited 22% and 25% local recurrence rates, 35% and 19% nodal metastasis rates, and 41% and 53% distant metastasis rates (median follow-up, 54 months and 39 months, respectively). The 5- and 10-year disease-specific survival rates were 88% and 43% and 52% and 42% (ES and USEF, respectively). TMA immunohistochemistry identified integrase interactor (INI)-1 loss, cancer antigen 125, and p53 nuclear expression as significantly more common in ES than USEF cases. Both cell lines preserved ES morphological and biochemical characteristics in vitro and in vivo; loss of INI-1 was shown to occur in both lines.Conclusions. Enhanced knowledge of ES and USEF clinical behavior, marker expression, and molecular determinants, extended via experimental models, will hopefully accelerate development of urgently needed effective targeted therapies for ES and USEF. The Oncologist 2011;16:512-522