Sensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin Increases its Potential as a Useful Serum Tumor Marker for Mesothelioma

Abstract

Background: Because mesothelioma initially progresses on the surface of the pleura and peritoneum without forming masses, it has been difficult to diagnose at an early stage. It would be very useful to identify a tumor marker that could be used for screening to enable more diagnoses to be made at an early, treatable stage. Materials and Methods: We had previously identified N-ERC/mesothelin as a potential biomarker for mesothelioma. In the current work, we used a newly developed ELISA system to gain data on N-ERC/mesothelin levels in various clinical settings. A total of 102 healthy volunteers were recruited. In addition, 39 patients were diagnosed with mesothelioma, 53 patients were diagnosed with diseases that should be distinguished from mesothelioma, and 201 subjects were diagnosed with asbestos-related nonmalignant diseases (including simple exposure to asbestosis) who were treated at any of the cooperating hospitals were enrolled. Results: Serum N-ERC/mesothelin levels measured by a new ELISA system showed that the median values from patients with mesothelioma were extremely high compared with levels obtained from other patients. Analysis in terms of histologic type showed that serum levels of N-ERC/mesothelin were elevated in epithelioid type mesothelioma, especially. In four important models of clinical settings, the sensitivity and specificity of N-ERC/mesothelin were about 71% to 90% and 88% to 93%, respectively. Conclusion: N-ERC/mesothelin is a very promising tumor marker for mesothelioma, especially epithelioid mesothelioma.Mesothelioma initially progresses along the surfaces of the pleura and peritoneum without forming masses; it is anatomically difficult to diagnose at an early stage and to completely remove with surgery. Moreover, mesothelioma typically has a long incubation period before it becomes clinically evident among high-risk individuals with severe exposure to asbestos. Sugarbaker et al.(1) has reported a groundbreaking result: for patients with early stage disease, 5-year survival after trimodality therapy exceeded 40%. This finding that early disease may be effectively treated emphasizes the importance of identifying a tumor marker that is practical for screening and can allow physicians to make an early diagnosis.Recently, osteopontin, soluble mesothelin-related protein, and serum mesothelin have been reported as candidates for a mesothelioma tumor marker (2 -7). We have postulated (8) that another product may be useful as a tumor marker: N-ERC/ mesothelin, a NH 2 terminal 31-kDa fragment of mesothelin gene products that was first cloned as a megakaryocytepotentiating factor in humans and that is physiologically secreted into blood. Since the time of that report, we have established a new ELISA system that detects the NH 2 terminal fragments of ERC/mesothelin products at a higher sensitivity and specificity. The current work was done to obtain data for Materials and MethodsPreparation of novel anti-ERC/mesothelin antibodies. The anti -N-ERC/mesothelin monoclonal antibody (Mo...

The utility of serum N-ERC/mesothelin as a biomarker of ovarian carcinoma

“…Serum samples were collected prior to surgery or chemotherapy from 11 patients and during chemotherapy against carcinomatous pleural effusion or ascites following surgery from 9. The cut-off levels of N and N(7-16) at 2.78 and 5.6 ng/ml, respectively, in the patients with mesothelioma have been previously reported (2). Of the 20 patients with ovarian tumors, one in the preoperative group showed increased N-ERC/mesothelin levels [N-ERC/mesothelin: N(7-4) = 4.76 ng/ml, N(7-16) = 18.67 ng/ml; Table I].…”

“…This protein is expressed on various malignant tumors, including mesothelioma and pulmonary, pancreatic and ovarian carcinomas. Recently, it has been recognized that the measurement of blood N-ERC/mesothelin levels aids early detection in and postoperative therapeutic monitoring of patients with mesothelioma, who have been exposed to asbestos (1)(2)(3).…”

Feasibility of large-scale screening using N-ERC/mesothelin levels in the blood for the early diagnosis of malignant mesothelioma

“…the sandwich EliSa system used in this report were established as described previously (3). the 7E7 moab was used as the capture antibody and the 16K16 moab was used as the detecting antibody after conjugation with horseradish peroxidase.…”

“…recently, soluble mesothelin-related protein (1) and serum mesothelin have been reported to be potentially useful markers for the early diagnosis of mm (2,3). a 71-kda precursor protein of human Erc/mesothelin can be cleaved into a 40-kda c-terminal fragment as a surface Gpi-anchored glycoprotein and a 31-kda n-terminal fragment as a secreted protein.…”

“…a 71-kda precursor protein of human Erc/mesothelin can be cleaved into a 40-kda c-terminal fragment as a surface Gpi-anchored glycoprotein and a 31-kda n-terminal fragment as a secreted protein. We focused on this n-Erc/ mesothelin, as it is physiologically secreted into the blood, and as a specific ELISA system has been developed for N-ERC/ mesothelin (2,3).…”