Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-Analysis

Hollevoet, Kevin; Reitsma, Johannes B.; Creaney, Jenette; Grigoriu, Bogdan; Robinson, Bruce; Scherpereel, Arnaud; Cristaudo, Alfonso; Pass, Harvey I.; Nackaerts, Kristiaan; Portal, José Antonio Rodríguez; Schneider, Joachim; Muley, Thomas; Serio, Francesca Di; Baas, Paul; Tomasetti, Marco; Alex, J.; Meerbeeck, Jan P. van

doi:10.1200/jco.2011.39.6671

Cited by 199 publications

(185 citation statements)

References 49 publications

(49 reference statements)

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“…The low sensitivity will not allow exclusion of non-MM patients even if they have mesothelin concentrations lower than the cutoff value. Thus, it would not be advisable to use a negative mesothelin test to exclude MM, even at a high-specificity threshold [70]. However, for the establishment of the optimal threshold, it should be taken into account that the diagnostic accuracy of the biomarkers depends on the distribution of individual characteristics, such as GFR, age, tumour stage and histology.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there is no agreement on the diagnostic thresholds of any of the above-mentioned biomarkers, because the reported ''optimal'' thresholds range widely [70]. The establishment of the ''optimal'' diagnostic thresholds is difficult as it depends on the distribution of the aforementioned characteristics of the study population.…”

Section: Effect Of Patient Characteristics On Mesothelin Mpf and Ostmentioning

confidence: 99%

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Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

et al. 2012

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Malignant mesothelioma (MM) is an aggressive tumour with poor prognosis whose early diagnosis is difficult. Mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin have attracted attention as biomarkers. The aim of the present review is to provide an overview regarding these candidate biomarkers for MM, and discuss their potential role in today's clinical practice.Mesothelin and MPF have good specificity but sub-optimal sensitivity for detection of MM, being negative both in the sarcomatoid histological sub-type and in almost half of epithelioid mesothelioma, especially in the early stages. Osteopontin is a marker of the duration of asbestos exposure, but lacks specificity for mesothelioma. Several patient characteristics influence the diagnostic accuracy of biomarkers and make the establishment of the ''optimal'' diagnostic threshold difficult. Mesothelin and MPF have proved useful in assessing response to treatment. Combining different markers together may lead to an improvement in diagnostic accuracy, but there is still need for research in this area. Extensive validation and further research is required to improve the use of serum markers in mesothelioma management. In the near future, their application in clinical practice is probably in monitoring response to therapy, rather than in guiding diagnostic decisions and risk assessment of asbestos-exposed populations.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Patient Characteristics On Mesothelin Mpf and Ostmentioning

confidence: 99%

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

et al. 2012

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“…On the other hand, surgical tumor reduction is followed by a decrease in SMRP levels 6,35,68 . Numerous studies have reported increased SMRP to be an independent prognostic factors for mesothelioma, with mesothelin levels negatively correlating with survival 31,36,37,63,71,74 . Another area of application of serum mesothelin measurement is monitoring of mesothelioma progression and its response to therapy, with SMRP being increased in disease progression and stable or decreasing SMRP levels being a sign of positive response to therapy 30,53,63,64,70,71,79 .…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have been performed to assess the utilization of mesothelin in the diagnosis of mesothelioma, reporting a sensitivity of 50-84% and specificity of 72-95% and statistically significantly higher SMRP levels in mesothelioma as compared with healthy exposed individuals or those with benign asbestos-induced conditions 30,31,35,55,[68][69][70][71][72] . Recent meta-analysis reported a sensitivity and specificity of SMRP for mesothelioma of 32-64% and 88-100%, respectively 73,74 . Another finding in many studies was statistically significantly higher mesothelin levels in mesothelioma than in metastatic involvement of the pleura but also statistically significantly higher mesothelin concentrations in metastatic pleural disease compared with asbestos-exposed individuals (healthy and/or with benign disease) (ref.…”

Section: Discussionmentioning

confidence: 99%

Significance of serum mesothelin in an asbestos-exposed population in the Czech Republic

Jakubec¹,

Pelclová²,

Smolková³

et al. 2015

BIOMED PAP

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Aims. Pleural mesothelioma is a highly aggressive and difficult-to-treat form of cancer induced by asbestos in 80-90% of cases. The population group most at risk of the condition are asbestos-exposed workers. Mesothelin or soluble mesothelin-related protein (SMRP) is studied as a potential marker of mesothelioma in the at-risk population. Methods. The study comprised 239 subjects with a mean duration of occupational exposure to asbestos of 19.9 years. In all of them, a complete medical history was taken, focused on exposure duration and a physical examination, a chest X-ray or other imaging investigations and a lung function test were performed. Their serum SMRP levels were measured and biopsy samples were taken to diagnose pleural disease. Based on the above examinations, the subjects were classified into subgroups and serum SMRP concentrations were statistically analyzed with respect to individual parameters. Results. In asbestos-exposed individuals, mesothelin levels were significantly higher in those with pathological X-ray findings than in those with normal X-ray results (0.78 ± 0.63 vs. 0.50 ± 0.35, P<0.0001). The group of patients with benign disease had statistically significantly higher mesothelin levels than those with normal X-ray findings (0.755 ± 0.543 vs. 0.50 ± 0.35, P<0.001). In the group with present malignant processes, mesothelin levels were higher than in individuals with benign disease (1.19 ± 0.89 vs. 0.76 ± 0.54, P=0.015). Only a weak correlation was found between mesothelin levels and asbestos exposure duration. There were relatively high sensitivity and high specificity (75% and 90.6%, respectively) of serum mesothelin for pleural mesothelioma. However, given the small number of mesothelioma cases in the group, the results cannot be considered as statistically significant. Conclusions. In persons followed up for asbestos exposure, increased mesothelin levels signalize pathological processes in the chest and correlate with severity of the disease. The study suggests that mesothelin cannot be considered a reliable marker for the early stage of malignant degeneration of pleural disease but only an additional criterion for examination of the followed-up individuals.

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“…Among less invasive procedures for the diagnosis, radiographic examinations such as chest roentgenogram and computed tomography (CT) are most commonly employed, but do not provide definitive diagnosis of MM. Blood-based tests may be promising, but the serum mesothelin related protein (SMRP), the only clinically approved blood-test, may not provide sufficient diagnostic sensitivity (8,9). Accordingly, a novel blood-based test for the diagnosis of MM should be established for early diagnosis as well as improvement of prognosis of MM patients.…”

Section: Introductionmentioning

confidence: 99%

Capture of mesothelioma cells with ‘universal’ CTC-chip

et al. 2017

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Abstract. Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.

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Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-Analysis

Cited by 199 publications

References 49 publications

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

Significance of serum mesothelin in an asbestos-exposed population in the Czech Republic

Capture of mesothelioma cells with ‘universal’ CTC-chip

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