Comparative immunohistochemical analysis of IMP3, GLUT1, EMA, CD146, and desmin for distinguishing malignant mesothelioma from reactive mesothelial cells

Our plain-English summary of Comparative immunohistochemical analysis of IMP3, GLUT1, EMA, CD146, and desmin for distinguishing malignant mesothelioma from reactive mesothelial cells, by H. Minato, N. Kurose, M. Fukushima, et al (American Journal of Clinical Pathology, 2014).

The study

• Authors: H. Minato, N. Kurose, M. Fukushima, T. Nojima, K. Usuda, M. Sagawa, T. Sakuma, A. Ooi, I. Matsumoto, M. Oda, Y. Arano, J. Shimizu
• Journal: American Journal of Clinical Pathology
• Published: 2014;141(1):85-93
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: To identify useful biomarkers for differentiating between malignant mesothelioma (MM) and reactive mesothelial cells (RMCs).

Methods: Formalin-fixed, paraffin-embedded (FFPE) tissues from 34 MM and 40 RMC samples were analyzed using immunohistochemistry, and the findings were compared.

Results: Positive markers for MM included insulin-like growth factor 2 messenger RNA binding protein 3 (IMP3), glucose transporter 1 (GLUT1), epithelial membrane antigen (EMA), and CD146, which showed sensitivities of 94%, 85%, 79%, and 71% and specificities of 78%, 100%, 88%, and 98%, respectively. In sarcomatoid MM, EMA had significantly lower expression than did IMP3, GLUT1, and CD146 (P < .001). The areas under receiver operating characteristic curves were the highest for IMP3 (0.95), followed by GLUT1 (0.93). When the optimal cutoff points for IMP3 (30%) and GLUT1 (10%) were used, the sensitivity of IMP3 and GLUT1 for MM was 100%, and the specificity of both for MM was 95%.

Conclusions: The combination of IMP3 and GLUT1 is most appropriate for distinguishing MM from RMC using FFPE sections.

In plain English

This laboratory study, from three hospitals in the Kanazawa area of Japan, tested whether five tissue stains could tell malignant mesothelioma apart from reactive (non-cancerous) mesothelial cells. The article does not discuss asbestos exposure. The authors stained stored tissue from 34 confirmed mesothelioma cases (31 pleural, 3 peritoneal) and from 40 benign lung samples from patients with pneumothorax, collected between 1998 and 2011. Sensitivity is the share of mesothelioma cases a stain flagged. Specificity is the share of benign samples it correctly left unflagged. Positive staining for IMP3, GLUT1, EMA and CD146 had sensitivities of 94%, 85%, 79% and 71% and specificities of 78%, 100%, 88% and 98%. IMP3 scored highest on the study's overall accuracy measure (0.95), followed by GLUT1 (0.93). Using IMP3 and GLUT1 together, with cutoffs of 30% and 10% of stained cells, gave 100% sensitivity and 95% specificity. EMA staining was significantly lower in the sarcomatoid type. The authors concluded that combining IMP3 and GLUT1 is most appropriate for this distinction. No diagnostically challenging cases were included, and the authors called for larger multi-institution studies.

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: Retrospective comparative immunohistochemical (tissue-staining) study of archived surgical pathology specimens
• Who was studied: 34 cases of malignant mesothelioma (31 pleural, 3 peritoneal; 17 epithelioid, 11 biphasic, 6 sarcomatoid; mean age 63, 31 men and 3 women) and 40 benign lung tissue samples with reactive mesothelial cells from patients with pneumothorax (mean age 39, 35 men and 5 women). The cases came from patients seen 1998 to 2011 at Kanazawa Medical University, Kanazawa University Hospital and KKR Hokuriku Hospital, Japan.
• Exposure: No asbestos or fiber exposure was studied or reported. The study tested five antibody stains (IMP3, GLUT1, CD146, EMA, desmin). A sample was called positive when more than 5% of cells stained.
• Main results:
  • For distinguishing mesothelioma from reactive mesothelial cells, positive staining for IMP3, GLUT1, EMA and CD146 had sensitivities of 94%, 85%, 79% and 71% and specificities of 78%, 100%, 88% and 98%, respectively.
  • As printed, negative desmin staining had 48% sensitivity and 97% specificity.
  • Area under the ROC curve (overall accuracy measure) was 0.95 for IMP3, 0.93 for GLUT1, 0.87 for EMA, 0.86 for CD146 and 0.73 for desmin.
  • Combining only IMP3 and GLUT1, with cutoffs of 30% for IMP3 and 10% for GLUT1, gave 100% sensitivity and 95% specificity.
  • With cutoffs of 40% for IMP3 and 0% for GLUT1, the combination gave both 100% sensitivity and 100% specificity.
  • In sarcomatoid mesothelioma, EMA expression was significantly lower than in epithelioid and biphasic types, compared with IMP3, GLUT1 and CD146 (P < .001).
  • All five mesothelioma cases negative for GLUT1 were positive for IMP3.
• The authors' conclusion: The authors concluded that the combination of IMP3 and GLUT1 is most appropriate for distinguishing malignant mesothelioma from reactive mesothelial cells in formalin-fixed, paraffin-embedded sections. They added that the combination may be very powerful when stromal invasion is difficult to assess.
• Limitations the authors state:
  • No diagnostically challenging cases were included.
  • The authors stated that larger multi-institution studies are needed to confirm the results, especially in diagnostically challenging cases.
  • The authors stated that the best methods and antibody clones for CD146 staining of paraffin-embedded tissue remain unclear.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: GLUT1, Desmin, Malignant Mesothelioma, Reactive Mesothelial Cells, Biomarker, Immunohistochemistry, Epithelial Membrane Antigen (EMA), Sarcomatoid.

Related studies

• 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 — K. Ikeda, G. Tate, et al. (2011)
• 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)
• 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)
• IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations — A.F. Lee, A.M. Gown, 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)
• Diagnostic value of BRCA1-associated protein-1, glucose transporter-1 and desmin expression in the discrimination between reactive mesothelial proliferation and malignant mesothelioma in tissues and effusions — S. Önder, E. Özogul, et al. (2019)

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