Mesothelin is a 40 kDa protein present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The protein was first identified by its reactivity with monoclonal antibody K1. Subsequent cloning studies showed that the mesothelin gene encodes a precursor protein that is processed to yield mesothelin which is attached to the cell membrane by a glycophosphatidylinositol linkage and a 31-kDa shed fragment named megakaryocyte-potentiating factor (MPF). Although it has been proposed that mesothelin may be involved in cell adhesion, its biological function is not known.
Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. Since mesothelin is overexpressed in several cancers and is immunogenic, the protein could be exploited as tumor marker or as the antigenic target of a therapeutic cancer vaccine.
Elevations of serum mesothelin specific to ovarian and other cancer patients may be measured using ELISA assays. Assays for blood-bourne mesothelin and MPF for tumor diagnosis, especially applied to asbestos-related mesothelioma have been developed. Elevated serum mesothelin was found in most patients with mesothelioma (71%) and ovarian cancer (67%). Blood MPF and mesothelin levels were correlated, with modest accuracy for malignant pleural mesothelioma and lung cancer (sensitivity 74% and 59%, specificity 90% and 86%, respectively for MPF and mesothelin assays). Circulating mesothelin is reported in nearly all pancreatic cancers, however the levels in healthy persons often exceed 80 ng/mL (using 40 kD molecular weight as the conversion factor) and to widely overlap the values in the pancreatic cancer patients. It was noted that the cutoff levels for normal could differ as much as 10-fold among publications, depending on the assay used (compare Sharon et al. and Iwahori et al. with Hassan et al.) and thus that normal levels must be determined anew when new assays are introduced.
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