Utility of glucose transporter 1 in the distinction of benign and malignant thoracic and abdominal mesothelial lesions

Our plain-English summary of Utility of glucose transporter 1 in the distinction of benign and malignant thoracic and abdominal mesothelial lesions, by S.M. Lagana, R.N. Taub, A.C. Borczuk (Archives of Pathology & Laboratory Medicine, 2012).

The study

• Authors: S.M. Lagana, R.N. Taub, A.C. Borczuk
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2012;136(7):804-9
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: Malignant mesothelioma, of either peritoneum or pleura, is an uncommon cancer. The diagnosis is often difficult to make, in part because of the overlapping morphology of reactive and malignant mesothelial cells. Glucose transporter 1 (GLUT-1) is a glucose transporter typically found on erythrocytes, which is aberrantly expressed in various carcinomas. It has recently been reported as specific and sensitive in discriminating malignant pleural mesothelioma from reactive hyperplasia. The application of GLUT-1 staining in peritoneal mesothelioma has not been fully explored.

Objective: To determine if GLUT-1 staining is helpful in distinguishing abdominal mesotheliomas from benign, reactive mesothelial lesions and to further study its utility in the thorax.

Design: Tissue microarrays containing 135 abdominal malignant mesotheliomas and 30 malignant pleural mesotheliomas were stained with an antibody to GLUT-1, as were 56 reactive mesothelial lesions.

Results: The overall sensitivity and specificity for GLUT-1 in mesothelioma was 53% and 98%, respectively. The sensitivity in epithelioid malignant mesothelioma was 49% and in sarcomatoid/biphasic malignant mesothelioma, 66%. In the thorax, the sensitivity was 50% and in the abdomen it was 54%. The positive predictive value of GLUT-1 immunoreactivity was 98% and the negative predictive value was 40%.

Conclusion: Glucose transporter 1 staining of thoracic mesotheliomas showed high specificity but lower sensitivity than previously reported. Abdominal malignant mesotheliomas showed similar results. Because of low sensitivity, only positive staining is informative. In both sites, the utility of the stain was limited by nonspecific staining (eg, in necrotic areas) as well as bright labeling of erythrocytes and occasional lymphoid elements. Despite these limitations, GLUT-1 can help differentiate malignant mesothelioma from reactive benign mesothelium.

In plain English

This study tested whether a laboratory stain for a protein called glucose transporter 1 (GLUT-1) helps pathologists tell malignant mesothelioma apart from benign, reactive mesothelial tissue. The authors stained archived tissue from Columbia University Medical Center, collected from 1998 to 2010. The samples included 30 thoracic (chest) mesotheliomas, 135 abdominal (peritoneal) mesotheliomas, and 56 benign reactive lesions used as controls. The study did not examine asbestos exposure. Overall, the stain was positive in 53% of the mesotheliomas. The authors reported 98% specificity, but 2 of 56 reactive controls stained positive, which is about 96%; the article does not explain this. Sensitivity was 50% in the chest and 54% in the abdomen, and higher in biphasic than in purely epithelioid cases (66% and 49%). The authors concluded that a positive stain strongly favors malignancy but a negative stain should not be considered informative. They reported that patchy staining, small biopsies, bright staining of red blood cells, and nonspecific staining in necrotic areas and lymphoid cells limit the test. They said it is best used with stains for mesothelial differentiation.

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 diagnostic study of archived pathology specimens, using immunohistochemical staining (mostly on tissue microarrays) to measure the sensitivity and specificity of GLUT-1
• Who was studied: Pathology cases from Columbia University Medical Center, New York, 1998–2010. Thoracic: 30 malignant mesotheliomas (21 epithelioid, 9 sarcomatoid or biphasic), with controls of 23 benign mesothelial hyperplasias and 15 fibrosing pleuritis cases. Abdominal: 135 malignant mesotheliomas (100 epithelioid, 35 biphasic or sarcomatoid), 3 well-differentiated papillary mesotheliomas, and 18 reactive mesothelial hyperplasia controls. In total there were 56 reactive mesothelial lesions
• Exposure: Not studied. The article did not assess asbestos or any other exposure; it tested a laboratory stain (an antibody to GLUT-1) on tissue samples
• Main results:
  • Across all mesotheliomas, the authors reported GLUT-1 sensitivity of 53% and specificity of 98%
  • The authors reported 2 false positives and gave specificity as 95% in the thorax and 100% in the abdomen. Two positives among the 56 reactive lesions works out to about 96%, not the 98% printed; the article does not explain the difference
  • Sensitivity was 50% in thoracic mesotheliomas (15 of 30 positive) and 54% in abdominal mesotheliomas
  • In the abdomen, 73 of 135 peritoneal mesotheliomas stained positive
  • Sensitivity was 66% in biphasic cases and 49% in purely epithelioid cases
  • One false positive was a mesothelial hyperplasia, called atypical and suspicious at the time, in a patient who was alive without evidence of malignancy one year after biopsy. The other was a case of fibrinous pleuritis with weak, focal staining
  • Positive predictive value was 98% and negative predictive value was 40%
• The authors' conclusion: The authors concluded that positive GLUT-1 staining was helpful in diagnosing malignancy in mesothelial proliferations. Because of limited sensitivity, a negative stain should not be considered informative, while a positive stain strongly favors malignancy. They said GLUT-1 staining is best performed together with stains for mesothelial differentiation
• Limitations the authors state:
  • Staining was sometimes patchy, with fewer than 10% of cells staining in 16 cases
  • The tissue microarrays were built to contain many tumor cells. Small biopsies may not contain as many, and patchy staining could then be detrimental
  • In biphasic cases, results in the two tumor components did not always agree
  • Strong staining of red blood cells could lead to false-positive or false-negative readings
  • Nonspecific staining in necrotic areas and staining of lymphoid cells could add confusion
  • No data on patients' ethnic background were collected, so the authors could not assess whether the differences from an earlier Japanese study reflect a biological difference

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Peritoneum, Pleura, Mesothelial Cells, Carcinoma, Pleural Mesothelioma, Peritoneal Mesothelioma, Thorax.

Related studies

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• IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations — A.F. Lee, A.M. Gown, 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)
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• Malignant mesothelioma presenting as a giant chest, abdominal and pelvic wall mass — Z.H. Shao, X.L. Gao, et al. (2011)

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