IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations

Our plain-English summary of IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations, by A.F. Lee, A.M. Gown, A. Churg (The American Journal of Surgical Pathology, 2013).

The study

• Authors: A.F. Lee, A.M. Gown, A. Churg
• Journal: The American Journal of Surgical Pathology
• Published: 2013;37(3):421-6
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Distinguishing malignant mesotheliomas from benign mesothelial proliferations on hematoxylin and eosin-stained sections can be extremely challenging. Various immunohistochemical stains have been suggested to help in making this distinction, but all are controversial. Recently, IMP3 (insulin-like growth factor II mRNA binding protein 3) and GLUT-1 (glucose transporter protein 1) have been proposed as immunohistochemical markers that are positive in mesotheliomas but not in benign proliferations. We evaluated the performance of these markers on a tissue microarray containing 30 malignant mesotheliomas and 48 benign thoracic or abdominal mesothelial proliferations. IMP3 was positive in 53% of malignant and 27% of benign cases (P=0.03), whereas GLUT-1 was positive in 60% of malignant and 13% of benign cases (P=0.0003). Forty-three percent of malignant cases, but only 4% of benign cases, were positive for both IMP3 and GLUT-1 (P=0.00003). We conclude that, statistically, both IMP3 and GLUT-1 are more frequently positive in malignant compared with benign mesothelial processes; however, the frequency of positive staining in benign cases is too high to allow their diagnostic use as single stains. The combination of both markers may be of greater diagnostic value, but this hypothesis should be confirmed in further studies.

In plain English

This study, from Vancouver, Canada, tested whether two laboratory stains, IMP3 and GLUT-1, can help pathologists tell malignant mesothelioma apart from benign (non-cancerous) growths of mesothelial cells. It did not examine asbestos exposure. The authors stained archived tissue from 30 malignant mesotheliomas (26 pleural, 3 peritoneal, 1 pericardial) and 48 benign mesothelial proliferations (27 pleural, 21 peritoneal), accessioned between 1997 and 2011. IMP3 was positive in 16 of 30 mesotheliomas (53%) and 13 of 48 benign cases (27%). GLUT-1 was positive in 18 of 30 mesotheliomas (60%) and 6 of 48 benign cases (13%). Both stains together were positive in 13 of 30 mesotheliomas (43%) but only 2 of 48 benign cases (4%). The authors concluded that both stains were positive more often in malignant cases, but stained too many benign cases to be used on their own. They wrote that combining the two might help, but called this only a hypothesis that other investigators need to test on independent cases. They also noted that requiring both stains to be positive lowered the share of mesotheliomas detected.

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 testing two immunohistochemical stains on archived tissue samples arranged in a tissue microarray
• Who was studied: 78 archived cases from the Vancouver General Hospital archives and the consultation files of one author (Canada), accessioned 1997 to 2011: 48 benign mesothelial proliferations (27 pleural, 21 peritoneal) and 30 malignant mesotheliomas (26 pleural, 3 peritoneal, 1 pericardial)
• Exposure: No asbestos or other fiber exposure was studied. What was tested was immunohistochemical staining for IMP3 (insulin-like growth factor II mRNA binding protein 3) and GLUT-1 (glucose transporter protein 1).
• Main results:
  • IMP3 was positive in 16/30 (53%) malignant mesotheliomas and 13/48 (27%) benign cases (P = 0.030); sensitivity 0.53, specificity 0.73
  • GLUT-1 was positive in 18/30 (60%) malignant mesotheliomas and 6/48 (13%) benign cases (P = 0.0003); sensitivity 0.60, specificity 0.88
  • Both stains together were positive in 13/30 (43%) malignant mesotheliomas and 2/48 (4%) benign cases (P = 0.00003); sensitivity 0.43, specificity 0.96
  • In cases with epithelial morphology, IMP3 was positive in 9/17 (53%) malignant and 12/39 (31%) benign cases, a difference that was not statistically significant (P = 0.14). GLUT-1 was positive in 9/17 malignant and 4/39 benign cases (P = 0.001). Both stains were positive in 7/17 malignant and 1/39 benign cases (P = 0.0005).
  • In cases with spindled morphology, both stains were positive in 6/14 (43%) malignant and 0/15 (0%) benign cases (P = 0.006). IMP3 alone was positive in 7/14 malignant and 2/15 benign cases, which the authors reported as not significantly different (P = 0.050). GLUT-1 alone was positive in 9/14 malignant and 2/15 benign cases (P = 0.008).
  • Staining intensity showed no obvious or consistent difference between benign and malignant cases
• The authors' conclusion: The authors concluded that, although both stains were statistically more often positive in malignant than benign cases, the rate of staining in benign cases (27% for IMP3, 13% for GLUT-1) makes each stain unsuitable for use on its own. They considered the combination of the two potentially helpful but unproven.
• Limitations the authors state:
  • The authors stated that the value of combining IMP3 and GLUT-1 is only a hypothesis that must be tested by multiple investigators on independent data sets
  • Using both markers improved specificity but lowered sensitivity, and a negative result for both does not show that a process is benign
  • Only 7 cases had mixed epithelial and spindled patterns, too few to analyze as a separate group, so they were counted in both the epithelial and spindled subgroups

Topics

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

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Malignant Mesothelioma, Mesothelioma.

Related studies

• 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)
• 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)
• 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)
• How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study — A.N. Husain, M.K. Mirza, et al. (2014)
• 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)

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