Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Cancer Cytopathol. 2014 Aug;122(8):586-95. doi: 10.1002/cncy.21439. Epub 2014 Jul 17.
The workup of a malignant effusion usually requires immunostaining with a panel of markers. Although nuclear Wilms tumor 1 (WT1) expression is widely used to detect tumors of ovarian and mesothelial origin, it is less well known that WT1 is also expressed in the cytoplasm of melanomas and mesenchymal tumors. Because to the authors' knowledge the diagnostic utility of cytoplasmic WT1 expression has not been explored to date, the usefulness of a WT1/AE1/AE3 dual-color immunostain in the workup of malignant effusions was evaluated.
A total of 86 pleural effusions, including 17 metastatic melanomas, 31 metastatic adenocarcinomas, 10 malignant mesotheliomas, 10 lymphoproliferative disorders, 5 metastatic sarcomas, and 13 benign specimens, were immunostained using a peroxidase-based brown chromogen for WT1 and an alkaline phosphatase-based red chromogen for AE1/AE3 on cell block sections.
The majority of malignant effusions stained in 1 of 4 distinctive patterns: 1) all lung and breast adenocarcinomas demonstrated cytoplasmic AE1/AE3 expression without nuclear or cytoplasmic WT1 expression; 2) serous carcinomas of Müllerian origin, mesotheliomas, and benign mesothelial cells were positive for cytoplasmic AE1/AE3 as well as nuclear WT1; 3) melanomas, sarcomas, and a subset of plasma cell neoplasms were positive for cytoplasmic expression of WT1 but negative for AE1/AE3; and 4) large B-cell lymphomas and a subset of plasma cell neoplasms were negative for both markers.
A WT1/AE1/AE3 dual-color immunostain can reliably identify malignancy in pleural effusions and group malignant cells into discrete subsets, thereby narrowing the differential diagnosis. This simple double stain can be a cost-effective, first-line test in the workup of patients with malignant effusions.
恶性胸腔积液的检查通常需要使用一组标志物进行免疫染色。虽然核 Wilms 肿瘤 1 (WT1)表达广泛用于检测卵巢和间皮来源的肿瘤,但较少为人知的是,WT1 也在黑色素瘤和间叶肿瘤的细胞质中表达。由于作者认为迄今为止尚未探讨细胞质 WT1 表达的诊断效用,因此评估了 WT1/AE1/AE3 双色免疫染色在恶性胸腔积液检查中的有用性。
对包括 17 例转移性黑色素瘤、31 例转移性腺癌、10 例恶性间皮瘤、10 例淋巴增生性疾病、5 例转移性肉瘤和 13 例良性标本的 86 例胸腔积液进行了细胞块切片的基于过氧化物酶的棕色显色剂 WT1 和基于碱性磷酸酶的红色显色剂 AE1/AE3 的免疫染色。
大多数恶性胸腔积液呈现出 4 种独特模式中的 1 种:1)所有肺和乳腺腺癌均显示细胞质 AE1/AE3 表达,而无核或细胞质 WT1 表达;2)Müllerian 来源的浆液性癌、间皮瘤和良性间皮细胞均为细胞质 AE1/AE3 以及核 WT1 阳性;3)黑色素瘤、肉瘤和一部分浆细胞瘤呈细胞质 WT1 阳性,但 AE1/AE3 阴性;4)大 B 细胞淋巴瘤和一部分浆细胞瘤则两种标志物均为阴性。
WT1/AE1/AE3 双色免疫染色可可靠地识别胸腔积液中的恶性肿瘤,并将恶性细胞分为离散亚群,从而缩小鉴别诊断范围。这种简单的双重染色可以成为检查恶性胸腔积液患者的一种具有成本效益的一线检测方法。