Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology.
Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology.
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DOI：
10.1038/modpathol.2015.87
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Gill AJ
中科院分区：
文献类型：
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作者：
Andrici J;Sheen A;Sioson L;Wardell K;Clarkson A;Watson N;Ahadi MS;Farzin M;Toon CW;Gill AJ
虽然大多数间皮瘤以胸腔积液为表现，但间皮瘤能否在胸腔积液细胞学上有把握地被诊断仍是有争议的。因此，作为恶性间皮细胞的辅助标志物在胸腔积液中的应用具有一定的临床价值。BRCA-1相关蛋白(BAP1)是一种肿瘤抑制基因，在大约一半的间皮瘤中表现出双等位基因失活。我们研究了免疫组织化学检测BAP1表达缺失是否可以用于积液细胞学中间皮瘤的诊断。对细胞块进行BAP1免疫组织化学染色，并解释为盲法。与确诊间皮瘤相关的75例积液中有43例(57%)呈阴性染色，而内对照呈阳性。在57例未明确诊断为间皮瘤的积液中，8例BAP1染色为阴性。在随访中，其中6名患者在随后的14个月内被确诊为间皮瘤(两名患者失去了立即随访，不能排除间皮瘤)。100例良性胸腔积液中，仅5例BAP1阴性。其中一名患者不久后死亡，不能排除间皮瘤。在非盲法回顾中，另外4例BAP1明显阴性但无恶性病变的患者在非肿瘤细胞中缺乏令人信服的阳性染色，这表明BAP1免疫组织化学最初可能被误解了。47例腺癌胸腔积液BAP1阳性。我们的结论是，BAP1的表达缺失，虽然不是决定性的，但可以用来支持渗出性细胞学中间皮瘤的诊断。我们警告说，在细胞块上解释BAP1免疫组织化学可能很困难，在认为非典型细胞为阴性之前，需要在非肿瘤细胞中进行令人信服的阳性染色。我们还注意到，BAP1缺失不是一项敏感的检测，因为它只发生在所有间皮瘤的一半，不能用来排除诊断。
Although most mesotheliomas present with pleural effusions, it is controversial whether mesothelioma can be diagnosed with confidence in effusion cytology. Therefore, an ancillary marker of malignant mesothelial cells applicable in effusions would be clinically valuable. BRCA-1-associated protein (BAP1) is a tumor suppressor gene, which shows biallelic inactivation in approximately half of all mesotheliomas. We investigated whether loss of BAP1 expression by immunohistochemistry can be used to support a diagnosis of mesothelioma in effusion cytology. Immunohistochemistry for BAP1 was performed on cell blocks and interpreted blinded. 43 of 75 (57%) effusions associated with confirmed mesothelioma showed negative staining with positive internal controls. Of 57 effusions considered to have atypical mesothelial cells in the absence of a definitive diagnosis of mesothelioma, 8 cases demonstrated negative staining for BAP1. On follow-up six of these patients received a definitive diagnosis of mesothelioma in the subsequent 14 months (two were lost to follow-up immediately, and mesothelioma could not be excluded). Only 5 of 100 consecutive benign effusions were interpreted as BAP1 negative. One of these patients died soon after and mesothelioma could not be excluded. On unblinded review the four other patients with apparently negative BAP1 staining but no malignancy lacked convincing positive staining in non-neoplastic cells suggesting that BAP1 immunohistochemistry may have initially been misinterpreted. 47 effusions with adenocarcinoma were BAP1 positive. We conclude that loss of BAP1 expression, while not definitive, can be used to support the diagnosis of mesothelioma in effusion cytology. We caution that interpretation of BAP1 immunohistochemistry on cell block may be difficult and that convincing positive staining in non-neoplastic cells is required before atypical cells are considered negative. We also note that BAP1 loss is not a sensitive test as it occurs in only half of all mesotheliomas and cannot be used to exclude the diagnosis.