A Limited Panel of Immunomarkers Can Reliably Distinguish Between Clear Cell and High-grade Serous Carcinoma of the Ovary
A Limited Panel of Immunomarkers Can Reliably Distinguish Between Clear Cell and High-grade Serous Carcinoma of the Ovary
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DOI：
10.1097/pas.0b013e3181788546
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发表时间：
2009-01-01
影响因子：
5.6
通讯作者：
Gilks, C. Blake
中科院分区：
文献类型：
--
作者：
Koebel, Martin;Kalloger, Steve E.;Gilks, C. Blake
区分卵巢透明细胞癌（CCCs）和高级别浆液性癌（HG-SCs）有时是一个诊断挑战。由于认识到CCCs对常规化疗的反应较差，人们开始努力开展CCCs的临床试验，这使得准确的诊断至关重要。本研究的目的是测试和验证一组抗体，这些抗体可以帮助诊断CCC，使用来自北美不同中心的一系列病例。使用133个CCCs的测试集，我们确定了以下标记物：Cyclin E、雌激素受体、肝细胞核因子(HNF)-1 β、Ki-67、p21、p53和Wilms tumor (WT)1，这些标记物与200个HG-SCs有显著区别。为了验证，这些标记物在来自其他3个中心的104个独立CCCs上进行了表征。这7个标记在CCC独立测试组和验证组之间的表达无显著差异。结合所有CCC病例（N = 237）， HNF-1 β对CCC的敏感性（82.5%）和特异性（95.2%）最高，WT1对HG-SC的敏感性（79.9%）和特异性（97.4%）最高。由WT1组成的诊断小组。ER和HNF-1 β在使用所有7种标记物区分CCCs和HG-SCs方面表现出几乎相同的表现，正确分类了84%的病例。3%的病例被错误分类，13%的病例携带不可靠的三阴性免疫表型。与HG-SCs相比，CCCs表现出独特的、可重复的免疫表型，在有问题的病例中，一组3种免疫标记物可作为诊断辅助。
The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition that CCCs respond poorly to conventional chemotherapy there are efforts to initiate clinical trials for CCC, making accurate diagnosis critical. The purpose Of this Study was to test and validate a set of antibodies that could aid in the diagnosis Of CCC, using a series of cases from different centers in North America. Using a test set of 133 CCCs, we identified the following markers: Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1 beta, Ki-67, p21, p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs. For validation, these markers were characterized on an independent set of 104 CCCs from 3 other centers. There were no significant differences in expression of these 7 markers between the independent test and validation sets of CCC. Combining all CCC cases (N = 237), HNF-1 beta showed the highest sensitivity (82.5%) and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%, specificity: 97.4%). A diagnostic panel consisting of WT1. ER, and HNF-1 beta demonstrated nearly identical performance as a panel using all 7 markers in distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three percent of cases were misclassified and 13% carried an uninformative triple negative immunophenotype. CCCs show a distinct, reproducible immunophenotype, compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic aid in problematic cases.