Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma

Abstract

Although immunohistochemistry has proven to be valuable in the differentiation of epithelioid mesothelioma from pulmonary or metastatic adenocarcinoma, no single antibody has demonstrated absolute sensitivity or specificity in making this distinction. Using immunohistochemical analysis with D2-40, a recently available monoclonal antibody that has been used as a lymphatic endothelial marker, we examined 53 cases of mesothelioma, 28 cases of reactive pleura, 30 cases of pulmonary adenocarcinoma, 35 cases of renal cell carcinoma, 26 cases of ovarian serous carcinoma, 16 cases of invasive breast carcinoma, 11 cases of prostatic adenocarcinoma, and seven cases of urothelial carcinoma. In addition, immunohistochemistry using calretinin, cytokeratin 5/6, and WT1 was performed on all cases of mesothelioma, pulmonary adenocarcinoma, ovarian serous carcinoma, and renal cell carcinoma. Predominantly, membranous D2-40 immunoreactivity was present in 51 of 53 (96%) mesotheliomas, 27 of 28 (96%) cases of reactive pleura, and 17 of 26 (65%) ovarian serous carcinomas; membranous staining was not seen in any other tumors examined. Compared to other immunohistochemical markers of mesothelioma, D2-40 was as sensitive as calretinin and more sensitive than cytokeratin 5/6 and WT1. We conclude that D2-40 immunoreactivity is sensitive for cells of mesothelial origin, and may be useful in the differential diagnosis of epithelioid malignant mesothelioma vs adenocarcinoma.

D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

“…5,7,15,[18][19][20]33 The D2-40 staining frequency is also controversial in sarcomatoid and biphasic malignant mesothelioma. Whereas Chu et al 23 reported staining in all types of malignant mesothelioma, Ordóñ ez 24 did not detect any D2-40 staining in either sarcomatoid malignant mesothelioma or sarcomatoid areas of biphasic malignant mesothelioma.…”

“…5,21,22 In addition to calretinin, D2-40 has been recently recommended as a new marker for malignant mesothelioma. 23,24 D2-40 is a novel monoclonal antibody that was reported to recognize a 40 kDa surface sialoglycoprotein expressed in germ cell neoplasia and fetal testicular gonocytes. 25 A recent investigation has demonstrated that this mucin-type glycoprotein is podoplanin.…”

“…29,30 Membranous staining of D2-40 has been described in 51 of 53 (96%) 23 and 29 of 40 (72%) malignant mesotheliomas. 24 No single antibody has demonstrated entire sensitivity or specificity for malignant mesothelioma, 5,22,23,[31][32][33][34] and an exact description of expression frequency in areas with sarcomatoid differentiation in sarcomatoid malignant mesothelioma or biphasic malignant mesothelioma has been largely neglected. The few publications that have evaluated calretinin expression in the three most frequent types of malignant mesothelioma separately present data that diverge from 18 to 100% positivity in sarcomatoid malignant mesothelioma, and 8 to 100% in biphasic malignant mesothelioma.…”

D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma

“…12 The broad application of D2-40 immunohistochemistry has established reactivity to multiple cell lineages and tumors such as mesothelioma, ovarian serous carcinoma, schwannoma, meningioma, synovial sarcoma, gastro-intestinal stromal tumor, leiomyosarcoma and others. [24][25][26] It is unknown whether D2-40 immunoreactivity in a wide spectrum of normal and neoplastic cells is due to a single protein expressed in these various tissues or results from a crossreactivity with multiple surface glycoproteins sharing the D2-40-recognized epitope defined by the common carbohydrate core. It is also unknown whether D2-40 reacts with the same or different antigens in normal lymphatics and in vascular tumor cells.…”

Immunophenotyping of serous carcinoma of the female genital tract

“…[10][11][12] D2-40, a marker of lymphatic endothelium as well as benign and malignant mesothelial cells, and a specific high molecular cytokeratin (CK) 5/6 were considered as useful 'mesothelioma markers'. [12][13][14][15] The aim of this study is to characterize the expression 'mesothelioma markers' and a panel of biological markers by serous tumors of the female genital tract and to explore possible variation in expression of markers among different sites.…”