Overexpression and altered glycosylation of MUC1 in malignant mesothelioma

Our plain-English summary of Overexpression and altered glycosylation of MUC1 in malignant mesothelioma, by J. Creaney, A. Segal, G. Sterrett, et al (British Journal of Cancer, 2008).

The study

• Authors: J. Creaney, A. Segal, G. Sterrett, M.A. Platten, E. Baker, A.R. Murch, A.K. Nowak, B.W. Robinson, M.J. Millward
• Journal: British Journal of Cancer
• Published: 2008;98(9):1562-9
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Current interest in the MUC1/EMA mucin relates to its role in malignancy, and its potential as a therapeutic target. MUC1/EMA expression has been observed in the majority of epithelioid mesotheliomas. However, little is known of the characteristics of MUC1/EMA in mesothelioma. Herein, we studied the cell surface and soluble expression of the MUC1/EMA glycoprotein, and determined the mRNA and genomic expression profiles in mesothelioma. We found that the anti-MUC1 antibody, E29, was the most diagnostically useful of seven antibody clones examined with a sensitivity of 84% (16 out of 19 cases) and no false positive results. MUC1 mRNA expression was significantly higher in mesothelioma samples than in benign mesothelial cells. No amplification of the MUC1 gene was observed by FISH. Seven of 9 mesothelioma samples expressed MUC1-secreted mRNA isoform in addition to the archetypal MUC1/transmembrane form. CA15.3 (soluble MUC1) levels were significantly higher in the serum of mesothelioma patients than in healthy controls but were not significantly different to levels in patients with benign asbestos-related disease. CA15-3 in effusions could differentiate malignant from benign effusions but were not specific for mesothelioma. Thus, as in other cancers, alterations in MUC1 biology occur in mesothelioma and these results suggest that specific MUC1 characteristics may be useful for mesothelioma diagnosis and should also be investigated as a potential therapeutic target.

In plain English

This laboratory study from Perth, Western Australia, examined a protein called MUC1 (also known as EMA) in samples from people with malignant mesothelioma, to see whether it could help with diagnosis. Samples came from the Australian Mesothelioma Tissue Bank. Comparison groups included people with benign pleural effusions, people with other cancers, healthy volunteers, and patients with asbestosis or with asbestosis and pleural plaques. Seven antibodies were tested on cells from pleural fluid. E29 stained 16 of 19 mesothelioma samples (84%) and gave no false positives. Mc5 stained every mesothelioma sample but had a 57% false-positive rate in benign samples. MUC1 gene activity was significantly higher in mesothelioma cells than in normal mesothelial cells, and this was not caused by extra copies of the gene. Blood levels of CA15-3, a soluble form of MUC1, were above normal in 17 of 49 mesothelioma patients and in 9 of 32 patients with benign asbestos-related disease. The difference between those two groups was not significant. The authors concluded that blood CA15-3 would not be a useful diagnostic aid and that MUC1-directed therapy should be investigated.

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 of patient samples, using antibody staining of effusion cells, gene-activity (PCR) tests, gene-copy (FISH) tests, and measurement of CA15-3 in serum and effusion fluid
• Who was studied: Samples from the Australian Mesothelioma Tissue Bank, Perth, Western Australia. Per Table 1 there were 60 mesothelioma patients (29 epithelial, 16 unspecified, 9 mixed, 6 sarcomatoid) and 39 patients with benign effusions. Controls were 7 normal mesothelial cell samples, 24 healthy volunteers, 11 asbestosis patients, 21 asbestosis patients with pleural plaques, and 26 patients with other cancers. Individual tests used subsets of these groups. Collection dates are not stated.
• Exposure: Asbestos exposure was not measured. The study measured MUC1/EMA, a cell protein, and CA15-3, its soluble form. Patients with asbestosis and pleural plaques served as a comparison group.
• Main results:
  • The E29 antibody stained 16 of 19 mesothelioma effusion samples (84%). Table 3 lists a 0% false-positive rate and specificity of 14/15 (93%) for E29 in benign reactive effusions.
  • E29 and four other antibody clones did not recognise MUC1 on benign mesothelial cells.
  • Across the seven antibodies, sensitivity for mesothelioma effusion samples ranged from 25% (VU2G7 and VU4H5) to 100% (Mc5).
  • The Mc5 antibody stained over half of the benign (nonmalignant) samples strongly, a 57% false-positive rate.
  • Activity of the transmembrane MUC1 gene was significantly greater in mesothelioma effusion and tumour samples than in normal mesothelial cells. Median levels were two to threefold greater in the mesothelioma samples.
  • FISH testing found no amplification (extra copies) of the MUC1 gene in mesothelioma samples. Seventeen samples were available, and the data were not shown.
  • About half of the mesothelioma samples, from solid tumour or effusions, also expressed a secreted form of MUC1. Normal mesothelial cells mainly expressed the full-length transmembrane form.
  • Serum CA15-3 was above the upper limit of normal (53 kU per litre) in 35% (17 of 49) of mesothelioma patients.
  • Serum CA15-3 was above the upper limit of normal in 28% (9 of 32) of patients with benign asbestos-related disease (asbestosis and/or pleural plaques). Serum CA15-3 did not differ significantly between mesothelioma patients and these patients.
  • Median serum CA15-3 was significantly higher in mesothelioma patients than in patients with benign effusions (P = 0.016) and healthy controls (P less than 0.0001).
  • In pleural effusion fluid, about 38% (20 of 52) of mesothelioma patients had CA15-3 above the upper limit of normal.
  • Effusion CA15-3 was elevated in 24% (6 of 25) of patients with cancers other than mesothelioma. Levels did not differ significantly between mesothelioma and these other cancers.
  • Effusion CA15-3 was significantly higher in mesothelioma patients than in patients with benign effusions (P = 0.004).
• The authors' conclusion: The authors concluded that because CA15-3 was also raised in patients with benign lung and pleural disease, serum CA15-3 will not be useful as a diagnostic aid for mesothelioma. They also suggested that MUC1-directed therapy in mesothelioma should be investigated.
• Limitations the authors state:
  • Patient numbers were limited for comparing serum CA15-3 across mesothelioma tissue types (sarcomatoid or mixed versus epithelioid).
  • The authors stated that the exact nature of the altered MUC1 glycosylation (sugar coating) in mesothelioma cells is unclear.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Epithelioid, Mesothelioma, Glycoprotein, Mesothelial Cells, Fluorescence In Situ Hybridization (FISH).

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)
• Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience — J.M. Porcel, C. Civit, et al. (2017)
• 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)
• 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)
• Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma — J. Creaney, A. Segal, et al. (2014)
• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)

Browse more research in British Journal of Cancer, or return to medical research.