Overexpression and altered glycosylation of MUC1 in malignant mesothelioma
Tuesday, May 6th, 2008.
Molecular Diagnostics. 2008 May 6;98(9):1562-9. Epub 2008 Apr 29. [Link]
Creaney J, Segal A, Sterrett G, Platten MA, Baker E, Murch AR, Nowak AK, Robinson BW, Millward MJ.
National Research Centre for Asbestos Related Diseases, Western Australian Institute of Medical Research, University of Western Australia, Perth, Western Australia, Australia. creaneyj@cyllene.uwa.edu.au
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.
Keywords: mesothelioma; MUC-1; EMA; diagnosis
Glossary
- gene
- a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.
- diagnosis
- identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- benign
- (be-nine) not cancer; not malignant.
- antibody
- a protein in the blood that defends against foreign agents, such as bacteria. These agents contain certain substances called antigens. Each antibody works against a specific antigen. (See also antigen.)
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
