Diagnostic usefulness of EMA, IMP3, and GLUT‐1 for the immunocytochemical distinction of malignant cells from reactive mesothelial cells in effusion cytology using cytospin preparations

Abstract

To differentiate reactive mesothelial cells (RMs) from metastatic carcinoma and malignant mesothelioma (MM) in effusion cytology is crucial for the cytologic diagnosis and the management of the patients. In the present study, the immunocytochemical staining profile of the epithelial membrane antigen (EMA), the insulin-like growth factor-II mRNA-binding protein 3 (IMP3), and the glucose transporter-1 (GLUT-1) was examined to distinguish RMs from malignant cells. A total of 171 pleural (n ¼ 87) and peritoneal (n ¼ 84) effusion specimens, including 50 benign effusions with RMs, 11 MM effusions, and 110 metastatic malignant effusions, were evaluated for immunocytochemistry. EMA, IMP3, monoclonal GLUT-1, and polyclonal GLUT-1 immunoreactivity were observed in 26.0%, 6.0%, 20.0%, and 18.0% of RMs, respectively. In contrast to RMs, the immunoreactivity in MM was 100%, 36.4%, 100%, and 90.9%; adenocarcinoma (AC) was 100%, 80.8%, 81.7%, and 72.1%; squamous-cell carcinoma was 83.3%, 83.3%, 83.3%, and 66.7%. EMA, IMP3, mGLUT-1, and pGLUT-1 expressions were observed in 98.4%, 65.6%, 88.5%, and 75.4% in the pleural effusion with malignant cells, and 100%, 88.3%, 78.3%, and 71.7% in ascites containing malignant cells, respectively. The findings of the present study indicate that the immunocytochemical staining for EMA, IMP3, and GLUT-1 is a useful diagnostic tool for distinguishing effusions containing malignant cells from those that contain benign cells, and in particular, we suggest that the combination of mGLUT-1 and EMA, and IMP3 and EMA are extremely useful in pleural effusion and in ascites, respectively. Diagn. Cytopathol. 2011;39:395-401. '

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.…”

Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: 2012 Update of the Consensus Statement from the International Mesothelioma Interest Group

“…Similar to histologic specimens (as discussed in other sections of this article), application of immunocytochemical and molecular techniques, either on smears or on cell blocks, enhances greatly the possibility to reach a correct diagnosis. 8,[14][15][16][17] Molecular techniques, such as fluorescence in situ hybridization (FISH) in demonstrat- 5 Acurio et al, 6 Shi et al, 8 Monaco et al, 20 and Attanoos et al…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…86,87 Multiple studies suggest that both epithelioid and sarcomatoid MMs are more likely to be positive for IMP3 (diffuse dark brown cytoplasmic staining), whereas reactive mesothelial proliferations are more likely to be negative for IMP3. [88][89][90][91] A consistent difference in staining intensity of IMP3 between benign and malignant proliferations has not been reported. 88 Overall, positive staining for IMP3 and/or GLUT1 may be helpful to confirm the diagnosis of malignancy; however, negative staining for IMP3 and/or GLUT1 does not completely rule out MM.…”