Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium

Abstract

Malignant pleural mesothelioma is a refractory tumor with poor prognosis associated with asbestos exposure. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective to detect malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of CD146, a cell adhesion molecule, has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. In this study, to evaluate the diagnostic utility of CD146 for discrimination between malignant pleural mesothelioma and reactive mesothelium, we examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity (0, negative; 1, weak positive; 2, moderate positive; and 3, strong positive). CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with median immunostaining score of 3 by OJ79, and in 19 of 21 malignant pleural mesothelioma with median immunostaining score of 2 by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208 and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by either OJ79 or EPR3208. On the other hand, CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 and 90%, respectively, and the specificity was 100% for both clones. We propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium.

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

“…65 Immunohistochemical markers used on histological samples to differentiate between benign and malignant mesothelial proliferation have also been used in cytology with similar unsatisfactory results. [28][29][30][31][32][33][34][35][36] The present study shows that the BAP1 profile of mesothelial cells is also easily identifiable on effusions and cell blocks. Benign mesothelial cells were invariably positive for BAP1, whereas 64% of mesotheliomas showed loss of protein; in equivocal cases by morphology, BAP1 negativity on mesothelial cells had a 100% positive predictive value for the diagnosis of mesothelioma: all six samples containing mesothelial cells negative for BAP1 were associated with a histological diagnosis of BAP1-negative mesothelioma.…”

Using of immunocytochemistry in differential diagnosis of neoplasms of serosal cavities in dogs

“…In diagnosing of mesothelioma it is necessary to use a panel of immunohistochemical stains (numerous antibodies should be used), since one immunostaining is not sufficient (Geninet et al 2003, Sato et al 2005, Reggeti et al 2005, Brisson et al 2006, Orgonez 2006, Hoinghaus et al 2008, Sato et al 2010. The need of using of the set of antibodies, especially those which are not routinely used in practical purposes, will lead to increase cost of the diagnostic procedure.…”

“…Therefore, besides specificity of antibodies in differentiation between visceral tumors, it is important to use these antibodies which are widely available and used in routine practice. Immunohistochemical staining of tissue samples from mesothelioma cells reveals the expression of cytokeratin, vimentin, podoplanin, carcinoembryonic antigen, calretinin, thrombomodulin, cadherins, desmin, CD15, CD146, and Ber-Ep4 (Geninet et al 2003, Sato et al 2005, Reggeti et al 2005, Brisson et al 2006, Orgonez 2006, Höinghaus et al 2008, Sato et al 2010. However, wide cross-reactivity with other tumors in at least some cases, in particular metastatic carcinoma has been found for all these markers, making their utility somewhat limited.…”

Utility of Immunohistochemistry in the Diagnosis of Pleuropulmonary and Mediastinal Cancers: A Review and Update

“…80,83 Initial exploration of the possibility of using CD146, a cell adhesion molecule, as a diagnostic marker for distinguishing MM from reactive mesothelial proliferation started a couple years ago, and few studies have been published. 84,85 One study performed by Sato et al 84 evaluated the expression of 2 clones of CD146 (OJ79 and EPR3208) in 23 pleural MMs and 28 reactive mesothelial proliferation cases. They found that the sensitivities of OJ79 and EPR3208 were 94% and 90%, respectively, and the …”