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PubMed2003

Novel markers of pancreatic adenocarcinoma in fine-needle aspiration: mesothelin and prostate stem cell antigen labeling increases accuracy in cytologically borderline cases.

The interpretation of pancreas fine-needle aspiration (FNA) is extremely difficult given the cytologic overlap of neoplastic and reactive processes. Using serial analysis of gene expression, we have discovered 2 new markers of pancreatic adenocarcinoma, mesothelin and prostate stem cell antigen (PSCA), and confirmed their specificity by immunohistochemical labeling. Here we evaluate the potential contribution of immunohistochemical labeling of mesothelin and PSCA to the interpretation of pancreas FNAs. Thirty pancreas FNAs with follow-up data were reviewed. Unstained cell block sections from these aspirates labeled for mesothelin and PSCA using immunohistochemistry were compared with initial cytologic diagnoses and with follow-up diagnoses. On follow-up, 19 patients proved to have cancer, and 11 did not. Initial cytologic diagnosis of malignancy correlated with carcinoma on follow-up in 12 of 12 cases, and initial benign cytologic diagnosis correlated with benign follow-up in 8 of 9 cases (sensitivity, 92%; specificity, 100%). Six of the 9 patients with suspicious cytology were found to have a carcinoma on follow-up. PSCA labeling was present in 16 of the 19 patients who ultimately were proven to have carcinoma; PSCA labeling was absent in 10 of the 11 lesions proven to be benign (sensitivity, 84%; specificity, 91%). Mesothelin labeling was present in 13 of the 19 patients who ultimately were proven to have carcinoma; mesothelin labeling was absent in 10 of the 11 lesions proven to be benign (sensitivity, 68%; specificity, 91%). Five of the 6 cytologically suspicious cases with malignant follow-up labeled for either PSCA or mesothelin (83%), and 2 of the 6 cases labeled for both markers. None of the 3 suspicious cases with benign follow-up labeled for either PSCA or mesothelin. Increasingly, molecular techniques are identifying potential cancer markers that may have diagnostic utility. In this study, immunohistochemical labeling for 2 of these markers, PSCA and mesothelin, appears highly specific for pancreatic adenocarcinoma in FNA specimens and useful in categorizing cytologically suspicious lesions.

Adenocarcinoma↗
PubMed2005

Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis.

Mesothelin, a cell surface glycoprotein present on normal mesothelial cells, has been reported to be expressed in pancreatic adenocarcinomas. We conducted this study to fully characterize mesothelin expression in surgically resected, formalin-fixed, paraffin-embedded tissue specimens of 18 pancreatic adenocarcinomas, 9 adenocarcinomas of the ampulla of Vater, 12 adenocarcinomas of the common bile duct, and 17 cases of chronic pancreatitis. Mesothelin immunostaining was performed using the antimesothelin monoclonal antibody 5B2. All 18 cases (100%) of pancreatic adenocarcinomas showed mesothelin expression, as did 8 (89%) of 9 cases of ampullar adenocarcinoma and all 12 cases (100%) of common bile duct adenocarcinoma. In all cases of pancreaticobiliary adenocarcinoma, the adjacent normal pancreas did not stain for mesothelin. Of 17 specimens of chronic pancreatitis, 16 were negative for mesothelin expression, and 1 case showed weak mesothelin staining of fewer than 5% of normal pancreatic ducts. Our results demonstrated mesothelin expression in the majority of pancreaticobiliary adenocarcinomas and no expression in normal pancreatic tissues and in chronic pancreatitis.

Adenocarcinoma↗
PubMedDate not supplied

Serum mesothelin in epithelial ovarian carcinoma: a new screening marker and prognostic factor.

UNLABELLED: The aim of this study was to determine the relationship between mesothelin and clinical pathological characteristics and whether mesothelin can be used as a biomarker for the detection and prognosis of epithelial ovarian carcinoma, or not. PATIENTS AND METHODS: Pre-operative mesothelin and CA125 levels from normal populations, patients with benign ovarian tumors and patients with ovarian carcinomas were measured. The histopathological characteristics and serum meosthelin, and CA125 levels influencing clinical outcome were evaluated comparatively. RESULTS: Mesothelin levels were higher in cancer patients than in those with benign ovarian tumors or in normal populations. Mesothelin, also significantly increased from early to advanced stages. Elevated mesothelin before therapy and advanced stage, revealed poorer overall survival (OS) for cancer patients. Elevated mesothelin before therapy also revealed poorer OS in cancer patients with optimal debulking surgery and in advanced-stage cancer patients. CONCLUSION: Mesothelin might be a new tumor marker for the differential diagnosis of epithelial ovarian carcinoma and a prognostic factorfor the outcome of epithelial ovarian carcinoma patients.

Adult↗
PubMed1997

Isolation of anti-mesothelin antibodies from a phage display library.

Phage display has been used to select single-chain Fvs (scFvs) against mesothelin, a surface antigen present on mesothelial cells as well as mesotheliomas and non-mucinous ovarian cancers. Several attempts to produce anti-mesothelin hybridomas from spleen cells of mice immunized with recombinant mesothelin were unsuccessful. This report describes the isolation of anti-mesothelin scFvs from a phage display library made from the mRNA of the same spleens. Panning on recombinant antigen produced in E. coli or on antigen positive cells was employed. Several scFvs which bind specifically to mesothelin were isolated. Panning on recombinant antigen yielded five different scFvs. Panning on cells selected two different scFvs which also differ from the scFvs selected by recombinant antigen. The heavy chains of the scFvs selected on recombinant antigen are derived from four different heavy chain gene families and the scFvs selected on cells are derived from two of these families. In contrast, the light chains of all of these scFvs are derived from family XI. Moreover, the light chains of the two scFvs selected on cells are very similar to the light chains of two of the scFvs selected by panning on recombinant mesothelin except for a few point mutations. One of these scFvs which have been studied in detail has been shown to bind specifically to mesothelin positive transfected cells.

3T3 Cells↗
PubMed2003

Value of mesothelin immunostaining in the diagnosis of mesothelioma.

Mesothelin is a cell surface antigen of unknown function that is strongly expressed in mesothelial cells. Although it was reported in 1992 that immunostaining with the K1 anti-mesothelin antibody could be very useful in distinguishing between epithelioid mesotheliomas and pulmonary adenocarcinomas, no further studies have been published on the value of this marker in the diagnosis of mesotheliomas. To determine whether mesothelin can assist in discriminating epithelioid mesotheliomas from lung adenocarcinomas or from other carcinomas metastatic to the serosal membranes, 55 mesotheliomas (44 epithelioid, 3 biphasic, and 8 sarcomatoid), 48 carcinomas of the lung (31 adenocarcinomas, 17 squamous carcinomas), and 86 nonpulmonary adenocarcinomas (14 ovary, 5 peritoneum, 9 endometrium, 11 pancreas, 4 stomach, 16 colon, 12 breast, 9 kidney, 4 thyroid, and 2 prostate) were investigated for mesothelin expression using the recently available 5B2 anti-mesothelin monoclonal antibody. Reactivity was obtained in all 44 (100%) of the epithelioid mesotheliomas, 12 (39%) of the lung adenocarcinomas, and 42 (49%) of the nonpulmonary adenocarcinomas (14 [100%] ovary; 5 [100%] peritoneum; 6 [67%] endometrium; 10 [91%] pancreas; 2 [50%] stomach; 5 [31%] colon; and in none [0] of the breast, kidney, thyroid, or prostate). Three (18%) of the squamous carcinomas of the lung, but none of the sarcomatoid mesotheliomas, exhibited positivity for this marker, nor was any reactivity seen in the spindle cell component of the biphasic mesotheliomas. It is concluded that despite the low specificity of mesothelin for discriminating between epithelioid mesotheliomas and adenocarcinomas, immunostaining for this marker may have some utility in those instances in which the results obtained with the standard panel of immunohistochemical markers used for the diagnosis of mesotheliomas are equivocal. Because mesothelin is a highly sensitive positive marker for epithelioid mesotheliomas, a negative staining for this marker is an indication against such a diagnosis; however, because of its limited utility, it is not recommended for inclusion in the standard panel of immunohistochemical markers used in the distinction between mesotheliomas and adenocarcinomas.

Adenocarcinoma↗
PubMed2005

[Expression and diagnostic value of mesothelin in specimen of pancreas fine-needle aspiration].

OBJECTIVE: To investigate the expression of mesothelin in specimen of pancreas fine-needle aspiration and to evaluate the potential contribution of immunohistochemical labeling of mesothelin to the interpretation of pancreas fine-needle aspiration (FNA). METHODS: Specimens from 27 patients were selected for immunolabeling. Immunohistochemical EnVision method was used to detect the expression of mesothelin in specimen of pancreas fine-needle aspiration. The labeling in each patient was scored as positive or negative. These results were compared with the cytologic diagnosis and the follow-up data. RESULTS: Nineteen of the 27 patients were ultimately shown to have an adenocarcinoma, and 8 had no evidence of malignancy on follow-up. Initial cytologic diagnosis of malignancy correlated with carcinoma on follow-up in 10 of 10 cases, and initial benign cytologic diagnosis correlated with benign follow-up in 4 of 6 cases. Seven of the 11 patients with suspicious cytology were found to have carcinomas on follow-up. Mesothelin labeling was seen in 14 of the 19 patients ultimately shown to have carcinomas and was absent in 7 of the 8 benign lesions (sensitivity, 73.7%; specificity, 87.5%). Five of the 7 cytologically suspicious cases with malignant follow-up labeled for mesothelin. Positive mesothelin labeling was observed in one of the 4 suspicious cases who finally proved to be benign during follow-up. CONCLUSION: Immunohistochemical labeling for mesothelin may be a highly specific tool for the detection of pancreatic adenocarcinoma in FNA specimens and is useful in categorizing cytologically suspicious lesions.

Adenocarcinoma↗
PubMedDate not supplied

Anti-tumor activity of K1-LysPE38QQR, an immunotoxin targeting mesothelin, a cell-surface antigen overexpressed in ovarian cancer and malignant mesothelioma.

Mesothelin, a differentiation antigen, is a 40-kD glycosylphosphatidylinositol-linked cell-surface glycoprotein, that is present on the surface of normal mesothelium and is overexpressed in many patients with epithelial ovarian cancer and malignant mesotheliomas. Monoclonal antibody K1 is a murine immunoglobulin G1 that recognizes mesothelin. LysPE38QQR is a truncated form of Pseudomonas exotoxin that lacks the cell-binding domain, but retains the translocation and adenosine diphosphate-ribosylation domains. It has a single lysine residue near the amino terminus that is available for conjugation to antibodies. To prevent chemical conjugation of the antibody to lysine residues at the C-terminus of Pseudomonas exotoxin, the two lysine residues at positions 590 and 606 were mutated to glutamine, and the lysine residue at position 613 was mutated to arginine. Monoclonal antibody K1 was chemically conjugated with LysPE38QQR, by modifying the antibody with sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate and coupling it with SPDP N-succinimidyl 3-(2-pyridyldithio)propionate-modified LysPE38QQR. The resulting immunotoxin K1-LysPE38QQR was highly toxic to A431-K5 cells (a human epidermoid carcinoma cell line transfected with a mesothelin expression plasmid) with a half-maximal inhibitory concentration of 3-6 ng/mL. The immunotoxin had negligible activity against A431 cells, which do not express mesothelin (median inhibitory concentration > 100 ng/mL). This immunotoxin also caused complete regression of tumors in nude mice that received xenografts of mesothelin-positive human carcinomas. These results show that immunotoxins directed against mesothelin are a therapeutic option that merits further investigation for the treatment of ovarian cancer and malignant mesotheliomas.

ADP Ribose Transferases↗
PubMed2006

Mesothelin variant 1 is released from tumor cells as a diagnostic marker.

The mesothelin family comprises (at least) three variants and includes the precursor for megakaryocyte potentiating factor (MPF). Assaying soluble mesothelin-related protein (SMRP) molecules in serum and other body fluids from patients with certain cancers can provide diagnostically useful information. We have constructed fusion proteins of mesothelin variants 1, 2, and 3, made monoclonal antibodies, and investigated the binding specificity of these and three previously generated monoclonal antibodies to each of the three mesothelin variants. According to flow cytometry, the molecule that is most frequently expressed at the surface of cells from ovarian carcinomas and certain other tumors is mesothelin variant 1. Similarly, SMRP released into ascites from a patient with ovarian carcinoma was shown to have a molecular weight of approximately 40 kDa and, according to sequencing, to be variant 1. A published sandwich ELISA was shown to detect variants 1 and 3 and to be much more sensitive than a newly constructed ELISA, which detects only variant 3, the former being positive in 28 of 41 (68%) sera from patients with ovarian cancer as compared with 6 of 41 sera (15%). A standard curve was constructed to measure SMRP with a limit of detection of 200 pg/mL to facilitate future quantitative studies.

Amino Acid Sequence↗
PubMed2006

Development of a CA125-mesothelin cell adhesion assay as a screening tool for biologics discovery.

Preventing peritoneal implantation of ovarian carcinoma cells could prolong patient remission and survival. CA125 is expressed on most ovarian cancer cells and was reported to be a ligand of mesothelin, a peritoneal protein. We developed a cell adhesion assay with CA125-expresser ovarian cancer cells and human mesothelin-transfected cells and we confirmed that CA125 and mesothelin mediate cell attachment. We also showed that this assay supplies a high-throughput screening system for reagents able to block CA125/mesothelin-dependent cell attachment with a sensitive quantitative readout. We finally demonstrated that a mesothelin chimeric protein and anti-CA125 antibodies block CA125/mesothelin-dependent cell attachment.

Antibodies, Monoclonal↗
PubMed2006

Real-time detection of mesothelin in pancreatic cancer cell line supernatant using an acoustic wave immunosensor.

BACKGROUND: An acoustic wave immunosensor was developed to illustrate the viability of such devices in early detection of molecular cancer biomarkers. The methods described here involve a real-time, less invasive technique for detecting mesothelin, a protein that has been linked to pancreatic and ovarian cancer. METHODS: Antibodies were immobilized on the gold surface of the device via a self-assembled alkanethiol monolayer. Supernatant from two different pancreatic cancer cell-lines (PL1 and CAPAN2) containing an unknown concentration of mesothelin was tested for the protein by a flow-through analytical technique in three types of experiments. Binding of the mesothelin to the immobilized antibody layer caused a shift in the device's resonant frequency, which was correlated to the concentration of supernatant. A reference sensor was used to correct for frequency shifts caused by pressure or viscosity effects from the injection of the supernatant solution. RESULTS: Repeated experiments indicate that the sensors are capable of nanogram detection thresholds of mesothelin proteins at room temperature and in complex mixture. CONCLUSIONS: Acoustic wave device biosensors have the potential to become a valuable tool in screening for pancreatic as well as other types of cancers. The main features include real-time detection, high sensitivity, and ease of use.

Antibodies, Monoclonal↗
PubMed2003

Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas.

The 40-kilodalton processed glycoprotein, mesothelin, is highly expressed in epithelial mesotheliomas and adenocarcinomas of the ovary (serous papillary) and pancreas, but its expression in a large series of other common carcinomas has not been completely explored. In the present study, we used oligonucleotide and tissue microarrays to profile the expression of the mesothelin gene (MSLN) and encoded protein, respectively. Among 150 carcinomas of multiple anatomic sites, we found the highest average expression of MSLN in serous carcinomas of the ovary and adenocarcinomas of the pancreas, consistent with previous reports, as well as measurable but less-striking expression in pulmonary, gastric/esophageal, and colorectal adenocarcinomas. On tissue microarrays containing 621 carcinomas derived from the same and additional sites as those profiled by gene expression, mesothelin immunoreactivity was highest in cancers of the ovary (serous papillary, endometrioid, and undifferentiated) and pancreas, with less frequent staining seen in adenocarcinomas of the endometrium, lung, and stomach/esophagus. Some immunopositivity was observed in 42% of pulmonary adenocarcinomas, including 18% that had >50% of tumor cells that were immunoreactive. Some 14% of breast and 30% of colorectal adenocarcinomas showed immunopositivity, but no case contained >50% tumor cells that were immunoreactive. Mesothelin was either entirely absent or present in <5% of carcinomas of the prostate, bladder/ureter, liver, kidney, and thyroid. Overall, we observed good concordance between the results obtained by oligonucleotide and tissue microarrays. This large study of the MSLN gene and protein expression in common carcinomas provides data for future investigations that evaluate the utility of mesothelin/megakaryocyte potentiating factor as a potential serum tumor marker or target of immunotoxin-based therapy in human cancers.

Biomarkers, Tumor↗
PubMed2006

Tumor-directed radiation and the immunotoxin SS1P in the treatment of mesothelin-expressing tumor xenografts.

PURPOSE: Mesothelin is a cell surface protein overexpressed in mesotheliomas and pancreatic and ovarian cancers. The goal of this study was to determine if radiation therapy in combination with the antimesothelin immunotoxin SS1(dsFv)PE38 (SS1P) would result in enhanced antitumor activity against mesothelin-expressing xenografts in nude mice. EXPERIMENTAL DESIGN: Female athymic nude mice bearing s.c. mesothelin-expressing xenografts were treated with SS1P alone, tumor-focused radiation alone, or the combination of the two. Two different regimens of the combination therapy were tested. In the low-dose combination schedule, mice were treated with either 5 Gy radiation alone, 0.2 mg/kg SS1P alone, or the same doses of radiation and SS1P in combination. In the high-dose combination experiments, mice were treated with either 15 Gy radiation alone, 0.3 mg/kg SS1P alone, or the combination of radiation and SS1P. RESULTS: In the low-dose radiation and SS1P combination studies, mice treated with the combination of radiation and SS1P had a statistically significant prolongation in time to tumor doubling or tripling compared with control, SS1P, or radiation alone. A similar increase in time to tumor doubling or tripling was seen in mice treated with high-dose radiation and SS1P combination. CONCLUSIONS: Combination of SS1P with tumor-directed radiation results in enhanced antitumor activity against mesothelin-expressing tumor xenografts. This effect was seen when either low or high doses of radiation were used.

Animals↗
PubMed1999

111Indium-labeled monoclonal antibody K1: biodistribution study in nude mice bearing a human carcinoma xenograft expressing mesothelin.

The monoclonal antibody (MAb) K1 is a murine IgG1 that recognizes mesothelin, a differentiation antigen present on mesothelium which is highly expressed on cancers derived from mesothelium, including most ovarian cancers and epithelioid mesotheliomas. MAb K1 was conjugated to 2-(p-isothiocyanatobenzyl)-cyclohexyl- diethylenetriaminepentaacetic acid and labeled with 111In. The biodistribution of 111In-K1 was studied in athymic nude mice bearing 2 s.c. tumors, one expressing a stably transfected plasmid encoding mesothelin and one composed of the parental untransfected A431 epidermoid carcinoma cells which do not express mesothelin. Tumor-bearing mice were given an i.v. injection of 111In-K1 and killed at different time points to determine the uptake of radiolabeled antibody. Significantly higher uptake was seen in antigen-positive tumors at all time points, with peak values at 72 hr (52.9% vs. 8% of the injected dose/g tissue for antigen-positive and antigen-negative tumors, respectively). Uptake in antigen-positive tumors was higher than the blood level at all time points, and the tumors contained a high level of the radiolabeled MAb even at 7 days (28.6% of the injected dose/g tumor).

Animals↗
PubMed2005

Forced expression of deltaN-TCF-1B in colon cancer derived cell lines is accompanied by the induction of CEACAM5/6 and mesothelin.

The colon cancer cell lines HT29 and SW480 were transfected with an N-terminal beta-catenin binding site-deficient high mobility group (HMG)-box T-cell factor 1 (deltaN-TCF-1) construct to identify differentially expressed genes. Oligonucleotide HG-U133A microarray expression profiling revealed increased mRNA levels of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5, 6 and mesothelin in transfectants positive for nuclear deltaN-TCF-1B. Increased amounts of CEACAM5 (CEA) were detectable in membrane-associated compartments, particularly in cholesterol-enriched microdomains. Similarly, mesothelin was demonstrated as an uncleaved membrane-bound constituent. The identified markers were examined in specimens of 46 colorectal carcinomas (CRC) by immunohistochemistry. Patchy areas of increased CEACAM5/6 staining were seen at the tumour-host front in all samples studied. Twenty-eight (58%) of these cases showed over-expression of mesothelin in a small fraction of tumor cells displaying dedifferentiation and dissemination at the invasion front. We conclude that forced expression of deltaN-TCF-1B in HT29 and SW480 is associated with up-regulation of GPI-anchored adhesion molecules, which were assigned to the tumour-host front in CRC patients.

Antigens, Neoplasm↗
PubMed2005

Expression of mesothelin, fascin, and prostate stem cell antigen in primary ovarian mucinous tumors and their utility in differentiating primary ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the ovary.

Metastatic pancreatic mucinous adenocarcinomas in the ovaries can be difficult to distinguish from primary ovarian mucinous neoplasms because the former can simulate the latter grossly and histologically and both tumor types share the same cytokeratin 7/cytokeratin 20 immunoprofile. We previously reported the utility of loss of Dpc4 expression in distinguishing metastatic pancreatic carcinomas from primary ovarian mucinous tumors. Recently several new pancreatic carcinoma markers have been identified, including mesothelin, fascin, and prostate stem cell antigen (PSCA). In this study we investigate the expression patterns of these markers in 35 primary ovarian mucinous tumors (28 atypical proliferative [borderline] tumors and 7 invasive carcinomas) and 11 metastatic pancreatic mucinous carcinomas in the ovary. Primary ovarian mucinous tumors expressed mesothelin (17%), fascin (26%), and PSCA (43%) less frequently than metastatic pancreatic adenocarcinomas (73%, 73%, and 82%, respectively). Expression of all three markers was seen only in metastatic pancreatic adenocarcinomas (45%), and coexpression of at least two markers was observed significantly more frequently in metastatic (82%) than primary ovarian mucinous tumors (17%). Our results indicate that an immunohistochemical panel including Dpc4, mesothelin, fascin, and PSCA is useful for evaluating difficult mucinous tumors in the ovary when the differential diagnosis includes metastatic pancreatic adenocarcinoma.

Adenocarcinoma, Mucinous↗
PubMed2005

Pretargeted radioimmunotherapy of mesothelin-expressing cancer using a tetravalent single-chain Fv-streptavidin fusion protein.

UNLABELLED: Mesothelin is a glycoprotein that is overexpressed in several human tumors, including mesotheliomas and ovarian cancers, and has been identified as a potential target for therapy. We evaluated the biodistribution and tumor-targeting ability of an antimesothelin tetravalent single-chain Fv-streptavidin fusion protein (SS1scFvSA) in mice. METHODS: SS1scFvSA was labeled with 125I or 111In for evaluation of internalization in vitro and for optimization of its biodistribution. The A431-K5 mesothelin transfected cell line was used as the target. We used a 3-step pretargeting approach consisting of injections of (i) SS1scFvSA, followed 20 h later by (ii) a synthetic clearing agent, and (iii) 4 h later, radiolabeled (111In, 88Y/90Y, or 177Lu) 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-biotin. To optimize the tumor uptake, the effect of the specific activity of 111In-DOTA-biotin was evaluated. RESULTS: Approximately 60% of SS1sc FvSA internalized within 6 h. The optimal dose of SS1scFvSA for pretargeting was 600 microg. Decreasing the specific activity of DOTA-biotin by administering 0.1-5 microg of DOTA-biotin resulted in tumor uptake decreasing from 31.8 to 5.5 %ID/g (percentage injected dose per gram) at 2 h. Pretargeted therapy of A431-K5 tumor with 90Y doses of 11.1-32.4 MBq resulted in a dose-dependent tumor response. With 32.4 MBq, 86% of mice survived tumor free for 110 d. All nontreated mice died, with a median survival of 16 d. CONCLUSION: SS1scFvSA localized in the mesothelin-expressing tumor, resulting in a high accumulation of radiolabeled DOTA-biotin. The specific activity of DOTA-biotin had a significant effect on its tumor uptake. Therapeutic tumor doses were obtained without dose-limiting toxicity.

Animals↗
PubMed2005

Soluble mesothelin-related protein--a blood test for mesothelioma.

Identification of tumor marker for mesothelioma (MM) might prove useful in diagnosis as well as for monitoring tumor in response to therapy and for screening at-risk individuals. We tested the hypothesis that soluble mesothelin-related protein (SMRP), a mesothelin family member, in the serum would be such a marker. Our data show that determination of SMRP in serum is a marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the first 48 MM patients tested. Changes in serum SMRP levels parallel clinical course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP should also be useful for monitoring disease progression, and importantly, may prove useful for screening asbestos-exposed individuals for early MM.

Adult↗
PubMed1996

Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers.

Monoclonal antibody MAb K1 recognizes a 40-kDa glycoprotein present on the surface of mesothelial cells, mesotheliomas, and ovarian cancers. We have used MAb K1 to isolate a 2138-bp cDNA that encodes this antigen. The cDNA has an 1884-bp open reading frame encoding a 69-kDa protein. When the cDNA was transfected into COS and NIH 3T3 cells, the antigen was found on the cell surface and could be released by treatment with phosphatidylinositol-specific phospholipase C. The 69-kDa precursor is processed to the 40-kDa form. The protein has been named mesothelin because it is made by mesothelial cells. Mesothelin may play a role in cellular adhesion.

Amino Acid Sequence↗