BAP1 Immunohistochemistry and p16 FISH to Separate Benign From Malignant Mesothelial Proliferations
BAP1 Immunohistochemistry and p16 FISH to Separate Benign From Malignant Mesothelial Proliferations
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DOI：
10.1097/pas.0000000000000394
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发表时间：
2015-07-01
影响因子：
5.6
通讯作者：
Churg, Andrew
中科院分区：
文献类型：
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作者：
Sheffield, Brandon S.;Hwang, Harry C.;Churg, Andrew
已有多种免疫组织化学(IHC)染色用于标记良性或恶性间皮细胞增殖。9p21纯合缺失的p16抑癌基因(CDKN2A)是间皮瘤的良好标志物，但缺乏敏感性。最近的报道表明，一些间皮瘤与BRCA相关蛋白1(BAP1)的表达缺失有关。在这里，我们研究BAP1和p16作为潜在的恶性肿瘤标记物，并使用特征良好的组织微阵列将检测特征与先前提出的标记物进行比较。免疫组织化学方法检测BAP1蛋白表达。用针对染色体9p21的荧光原位杂交(FISH)方法检测p16基因座。26例间皮瘤中7例BAP1缺失，49例良性增生症中0例BAP1缺失。在27例间皮瘤和40例良性增生性病变中，14例p16基因缺失，其特异性和阳性预测值均为100%。BAP1、IHC和p16 FISH联合检测恶性肿瘤的敏感性为58%。P53、EMA、IMP3和GLUT1的不同组合显示出相当高的特异度(96%到98%)，但敏感性很差到非常差。BAP1IHC/p16 FISH联合检测是诊断恶性间皮瘤的一种高度特异的方法，当问题是间皮细胞增殖是良性还是恶性时，尤其在无法证明间皮细胞侵袭组织时特别有用。然而，联合检测BAP1/p16 FISH不是高度敏感的，阴性结果不能排除间皮瘤。先前提出的标记物EMA、P53、GLUT1、IMP3的测试特征表明，即使组合使用，这些标记物在临床环境中也不是有用的工具。
A variety of immunohistochemical (IHC) stains have been proposed to mark either benign or malignant mesothelial proliferations. Loss of the p16 tumor suppressor (CDKN2A), through homozygous deletions of 9p21, is a good marker of mesotheliomas but lacks sensitivity. Recent reports indicate that some mesotheliomas are associated with loss of BRCA-associated protein 1 (BAP1) expression. Here we investigate BAP1 and p16 as potential markers of malignancy and compare test characteristics with previously proposed markers using a well-characterized tissue microarray. BAP1 protein expression was interrogated by IHC. The p16 locus was examined by fluorescence in situ hybridization (FISH) directed toward chromosome 9p21. Loss of BAP1 was identified in 7/26 mesotheliomas and 0/49 benign proliferations. Loss of p16 was identified in 14/27 mesotheliomas and 0/40 benign proliferations, yielding 100% specificity and positive predictive value for each marker. Together, BAP1 IHC and p16 FISH were 58% sensitive for detecting malignancy. Various combinations of p53, EMA, IMP3, and GLUT1 showed reasonably high specificity (96% to 98%) but poor to extremely poor sensitivity. Combined BAP1 IHC/p16 FISH testing is a highly specific method of diagnosing malignant mesotheliomas when the question is whether a mesothelial proliferation is benign or malignant and is particularly useful when tissue invasion by mesothelial cells cannot be demonstrated. However, combined BAP1/p16 FISH testing is not highly sensitive, and negative results do not rule out a mesothelioma. The test characteristics of previously proposed markers EMA, p53, GLUT1, IMP3 suggest that, even in combination, these markers are not useful tools in this clinical setting.