传统内皮标志物在胸膜间皮瘤中的频繁表达：紧密连接蛋白-5以及联合传统标志物在鉴别间皮瘤与血管肉瘤中的作用

Frequent expression of conventional endothelial markers in pleural mesothelioma: usefulness of claudin-5 as well as combined traditional markers to distinguish mesothelioma from angiosarcoma.

作者信息

Nakashima Yasuhiro, Inamura Kentaro, Ninomiya Hironori, Okumura Sakae, Mun Mingyon, Kirimura Susumu, Kobayashi Masashi, Okubo Kenichi, Ishikawa Yuichi

机构信息

Division of Pathology, The Cancer Institute, Departments of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan; Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.

Division of Pathology, The Cancer Institute, Departments of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.

出版信息

Lung Cancer. 2020 Oct;148:20-27. doi: 10.1016/j.lungcan.2020.07.029. Epub 2020 Jul 30.

DOI:10.1016/j.lungcan.2020.07.029

PMID:32777673

Abstract

OBJECTIVES

Distinguishing pleural sarcomatoid mesotheliomas from true sarcomas is challenging because the former does not always express the mesothelial markers, and diagnosis is often made on the basis of keratin expression. Consequently, sarcomas such as angiosarcomas that express keratin complicate the differential diagnosis. Furthermore, some mesotheliomas have been reported to express endothelial markers. The aim of this study is to identify useful markers for distinguishing pleural sarcomatoid mesothelioma from angiosarcoma.

MATERIALS AND METHODS

This study enrolled 147 patients with pleural mesothelioma-93 with epithelioid, 25 with biphasic, and 29 with sarcomatoid subtypes-and 41 patients with angiosarcomas in various organs. The expression levels of cytokeratin, mesothelial, and endothelial markers were assayed in both groups to identify the markers that could assist in distinguishing mesothelioma from angiosarcoma. Cytokeratin (AE1/AE3, CAM 5.2), endothelial (CD31, CD34, ERG, factor VIII, and claudin-5), and mesothelial (calretinin, WT-1, podoplanin (D2-40), EMA, and CK5/6) markers were immunohistochemically assayed using tissue blocks.

RESULTS

More than 90% of the mesotheliomas and less than 20% of the angiosarcomas expressed cytokeratin. Calretinin was expressed in 82% of all types of mesotheliomas but in only 48% of sarcomatoid mesotheliomas. Endothelial markers were expressed in mesothelioma tissues-CD31 in 10.3%, CD34 in 3.5%, ERG in 29%, and factor VIII in 3.4%-and the positivity was higher in sarcomatoid than in epithelioid and biphasic mesotheliomas. Claudin-5 was expressed in all the angiosarcomas, but not in any of the mesotheliomas.

CONCLUSION

We found overlapping immunophenotypes in pleural mesotheliomas and angiosarcomas, but the sensitivity and specificity of claudin-5 expression were sufficient to distinguish between them. The differential diagnosis of mesothelioma should therefore include claudin-5 in a panel of immunohistochemical markers to distinguish mesothelioma from angiosarcoma.

摘要

目的

鉴别胸膜肉瘤样间皮瘤与真性肉瘤具有挑战性，因为前者并不总是表达间皮标志物，诊断往往基于角蛋白表达。因此，诸如表达角蛋白的血管肉瘤等肉瘤会使鉴别诊断变得复杂。此外，有报道称一些间皮瘤表达内皮标志物。本研究的目的是确定有助于鉴别胸膜肉瘤样间皮瘤与血管肉瘤的有用标志物。

材料与方法

本研究纳入了147例胸膜间皮瘤患者——93例上皮样、25例双向性和29例肉瘤样亚型——以及41例各器官血管肉瘤患者。检测两组中细胞角蛋白、间皮和内皮标志物的表达水平，以确定有助于鉴别间皮瘤与血管肉瘤的标志物。使用组织块通过免疫组织化学方法检测细胞角蛋白（AE1/AE3、CAM 5.2）、内皮标志物（CD31、CD34、ERG、因子VIII和claudin-5）以及间皮标志物（钙视网膜蛋白、WT-1、足板蛋白（D2-40）、上皮膜抗原和CK5/6）。

结果

超过90%的间皮瘤和不到20%的血管肉瘤表达细胞角蛋白。钙视网膜蛋白在所有类型间皮瘤中的表达率为82%，但在肉瘤样间皮瘤中仅为48%。内皮标志物在间皮瘤组织中有表达——CD31为10.3%，CD34为3.5%，ERG为29%，因子VIII为3.4%——肉瘤样间皮瘤中的阳性率高于上皮样和双向性间皮瘤。Claudin-5在所有血管肉瘤中均有表达，但在任何间皮瘤中均未表达。