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

Our plain-English summary of 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, by K. Ikeda, G. Tate, T. Suzuki, et al (Diagnostic Cytopathology, 2011).

The study

• Authors: K. Ikeda, G. Tate, T. Suzuki, T. Kitamura, T. Mitsuya
• Journal: Diagnostic Cytopathology
• Published: 2011;39(6):395-401
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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 = 87) and peritoneal (n = 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.

Copyright © 2010 Wiley-Liss, Inc.

In plain English

This laboratory study tested whether staining for three proteins could help tell cancer cells apart from benign 'reactive' mesothelial cells in fluid from around the lungs (pleural effusion) or in the abdomen (peritoneal effusion). The authors stained 171 specimens (87 pleural, 84 peritoneal): 50 benign effusions, 11 epithelial malignant mesothelioma effusions and 110 effusions from cancers that had spread from other organs. The stains were EMA, IMP3 and GLUT-1, the last detected with both a monoclonal and a polyclonal antibody. Asbestos exposure was not studied. EMA stained 26.0% of benign specimens (13/50) and all 11 mesotheliomas. IMP3 stained 6.0% of benign specimens (3/50) but only 36.4% of mesotheliomas (4/11). Monoclonal GLUT-1 stained 20.0% of benign specimens (10/50) and all 11 mesotheliomas. EMA was the most sensitive marker (99.2%) and IMP3 the most specific (94.0%). The authors concluded that the stains are useful for separating malignant from benign effusions but not for telling mesothelioma from adenocarcinoma. They recommended EMA with monoclonal GLUT-1 for pleural fluid and EMA with IMP3 for abdominal fluid.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory diagnostic study comparing immunocytochemical stains on effusion (body-fluid) specimens
• Who was studied: 171 effusion specimens: 87 pleural and 84 peritoneal. They comprised 50 benign effusions with reactive mesothelial cells (from patients with no history of malignancy and no malignant cells found), 11 epithelial malignant mesothelioma effusions (10 pleural, 1 peritoneal) and 110 metastatic malignant effusions (mostly adenocarcinomas of ovary, stomach, lung and other organs, plus 6 squamous-cell carcinomas).
• Exposure: No asbestos exposure was studied. The 'exposure' was staining of 95% alcohol-fixed cytospin smears (using a cell-transfer technique) for EMA, IMP3, and GLUT-1 detected with a monoclonal antibody (mGLUT-1) and a polyclonal antibody (pGLUT-1).
• Main results:
  • EMA staining was positive in 26.0% of reactive mesothelial cell specimens (13/50), 100% of epithelial mesothelioma (11/11), 100% of adenocarcinoma (104/104) and 83.3% of squamous-cell carcinoma (5/6) specimens.
  • IMP3 staining was positive in 6.0% of reactive mesothelial cell specimens (3/50), 36.4% of epithelial mesothelioma (4/11) and 80.8% of adenocarcinoma (84/104) specimens. Its specificity for malignant effusions was 94.0% and its sensitivity 76.9%.
  • Monoclonal GLUT-1 staining was positive in 20.0% of reactive mesothelial cell specimens (10/50), 100% of epithelial mesothelioma (11/11) and 81.7% of adenocarcinoma (85/104) specimens.
  • Polyclonal GLUT-1 staining was positive in 18.0% of reactive mesothelial cell specimens (9/50), 90.9% of epithelial mesothelioma (10/11) and 72.1% of adenocarcinoma (75/104) specimens.
  • For malignant effusions, specificity was 80.0% for monoclonal GLUT-1 and 82.0% for polyclonal GLUT-1. Sensitivity was 83.5% and 73.6%, respectively.
  • IMP3 was the most specific marker for malignant cells in effusions (94.0%), and EMA was the most sensitive (99.2%). EMA's overall specificity was 74.0%.
  • When EMA was counted as positive only if more than 10% of cells stained, its specificity rose to 86.0% and its sensitivity did not change.
  • When IMP3 was counted as positive only if more than 10% of cells stained, its specificity rose to 98.0% and its sensitivity did not change.
  • In malignant pleural effusions, EMA, IMP3, monoclonal GLUT-1 and polyclonal GLUT-1 were positive in 98.4%, 65.6%, 88.5% and 75.4% respectively. In malignant ascites the figures were 100%, 88.3%, 78.3% and 71.7%.
  • Red blood cells stained strongly for GLUT-1, and heavy background staining occurred when many red blood cells were present.
• The authors' conclusion: The authors concluded that staining for EMA, IMP3 and GLUT-1 is a useful diagnostic tool for distinguishing malignant from benign effusions, but not for distinguishing malignant mesothelioma from adenocarcinoma. They recommended combining monoclonal GLUT-1 and EMA for pleural effusions and IMP3 and EMA for ascites.
• Limitations the authors state:
  • The authors stated that, although EMA stained malignant cells more strongly than reactive mesothelial cells, a diagnosis should not be made on staining intensity alone.
  • The authors noted that EMA is less specific than IMP3 and both forms of GLUT-1.
  • Normal endometrial cells, often seen in peritoneal washing samples, stained positive for EMA.
  • The authors noted that neither the monoclonal nor the polyclonal GLUT-1 antibody showed high specificity.
  • IMP3 staining was lowest in lung cancer, breast cancer and mesothelioma effusions. The authors advised against using it for pleural effusions.

Topics

Medical terms in this study, explained in our Lexicon: Reactive Mesothelial Cells, Cytology, Carcinoma, Malignant Mesothelioma, Epithelial Membrane Antigen (EMA), Monoclonal, Adenocarcinoma, Pleural Effusion.

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• Comparative immunohistochemical analysis of IMP3, GLUT1, EMA, CD146, and desmin for distinguishing malignant mesothelioma from reactive mesothelial cells — H. Minato, N. Kurose, et al. (2014)
• Value of Glut-1 and Koc markers in the differential diagnosis of reactive mesothelial hyperplasia, malignant mesothelioma and pulmonary adenocarcinoma — Ö. Üçer, A.F. Dağli, et al. (2013)
• Distinguishing benign from malignant mesothelial cells in effusions by Glut-1, EMA, and Desmin expression: an evidence-based approach — M. Kuperman, R.R. Florence, et al. (2013)
• Practical utility of insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1, and epithelial membrane antigen for distinguishing malignant mesotheliomas from benign mesothelial proliferations — S. Chang, M.H. Oh, et al. (2014)
• IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations — A.F. Lee, A.M. Gown, et al. (2013)

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