Malignant Mesothelioma Diagnosis

Arif, Qudsia; Husain, Aliya N.

doi:10.5858/arpa.2013-0381-ra

Cited by 37 publications

(33 citation statements)

References 20 publications

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“…A major difficulty of our record linkage study consisted in selecting a cohort of cases with a high probability of being PM, since a valid diagnosis of PM is complex [9, 10, 20, 27, 28]. The main problem was to distinguish mesothelioma from cancer of the lung invading the pleura or from pleural metastases of other primary tumors.…”

Section: Discussionmentioning

confidence: 99%

Management and Survival of Pleural Mesothelioma: A Record Linkage Study

et al. 2018

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Background: Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management has yet to be established. Objectives: To assess management, overall survival (OS), and their predictors in a cohort of patients from Lombardy, the largest Italian region (about 10 million inhabitants). Methods: Through a record linkage between Lombardy health care administrative databases, we identified patients diagnosed with PM in 2006–2011 without history of cancer, evaluating their management. OS from PM diagnosis was estimated using the Kaplan-Meier method. Predictors of OS and of treatment were assessed using Cox regression models with time-dependent covariates when appropriate. Results: Out of 1,326 patients, 754 (56.9%) received treatment for PM: 205 (15.5%) underwent surgery, and 696 (52.5%) used chemotherapy. Surgery was spread across several hospitals, and most patients diagnosed in nonspecialized centers (70%) underwent surgery in the same centers. Age at diagnosis was a strong inverse determinant of surgery. Determinants of receiving chemotherapy were younger age, a more recent first diagnosis, and first diagnosis in a specialized center. OS was 45.4% at 1 year, 24.8% at 2 years, and 9.6% at 5 years (median 11 months). OS decreased with age, and was higher for those who underwent surgery, but not for those treated with chemotherapy. Conclusions: Management of PM varied widely in clinical practice, and significant predictors of treatment were younger age and recent diagnosis, though a high proportion of patients were not treated. Patients were treated in various hospitals, indicating the importance of concentrating serious rare neoplasms in Comprehensive Cancer Centers (as recognized by the Italian Health Ministry).

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Section: Discussionmentioning

confidence: 99%

Management and Survival of Pleural Mesothelioma: A Record Linkage Study

et al. 2018

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“…Using primary cells from a mouse model Blum et al demonstrated that mesothelial cell proliferation and migration was increased or decreased by overexpression or absence of calretinin, respectively, hinting at a possible target for a new therapeutic approach [13]. Calretinin is extensively used in antibody panels for the clinical diagnosis of MM by immunohistochemistry, including the sarcomatoid subtype [5, 11, 14, 15]. We found, in a small number of samples, that soluble calretinin was elevated in the blood of individuals with MM relative to healthy and asbestos-exposed controls [9].…”

Section: Introductionmentioning

confidence: 99%

Calretinin as a blood-based biomarker for mesothelioma

et al. 2017

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BackgroundMalignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin.MethodsFor a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype.ResultsCalretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10–3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30–4.00).ConclusionsCalretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3375-5) contains supplementary material, which is available to authorized users.

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“…The protein mesothelin has been described as an absolutely promising biomarker, because its altered levels in serum and pleural fluid are usually associated with MPM, however, in spite of its high specificity, its sensitivity is low [12, 13]. In addition, the deletion of CDKN2A and BAP1 are the most common genetic alterations in MPM [14] and for this reason they have been suggested as diagnostic and prognostic markers. The FISH analysis of CDKN2A and the immunohistochemistry analysis of BAP1 could enable the differential diagnosis of benign and malignant mesothelial proliferations, either alone or together [15].…”

Section: Introductionmentioning

confidence: 99%

Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis

et al. 2016

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Malignant pleural mesothelioma (MPM) is a rare asbestos related cancer, aggressive and unresponsive to therapies. Histological examination of pleural lesions is the gold standard of MPM diagnosis, although it is sometimes hard to discriminate the epithelioid type of MPM from benign mesothelial hyperplasia (MH).This work aims to define a new molecular tool for the differential diagnosis of MPM, using the expression profile of 117 genes deregulated in this tumour.The gene expression analysis was performed by nanoString System on tumour tissues from 36 epithelioid MPM and 17 MH patients, and on 14 mesothelial pleural samples analysed in a blind way. Data analysis included raw nanoString data normalization, unsupervised cluster analysis by Pearson correlation, non-parametric Mann Whitney U-test and molecular classification by the Uncorrelated Shrunken Centroid (USC) Algorithm.The Mann-Whitney U-test found 35 genes upregulated and 31 downregulated in MPM. The unsupervised cluster analysis revealed two clusters, one composed only of MPM and one only of MH samples, thus revealing class-specific gene profiles. The Uncorrelated Shrunken Centroid algorithm identified two classifiers, one including 22 genes and the other 40 genes, able to properly classify all the samples as benign or malignant using gene expression data; both classifiers were also able to correctly determine, in a blind analysis, the diagnostic categories of all the 14 unknown samples.In conclusion we delineated a diagnostic tool combining molecular data (gene expression) and computational analysis (USC algorithm), which can be applied in the clinical practice for the differential diagnosis of MPM.

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Malignant Mesothelioma Diagnosis

Cited by 37 publications

References 20 publications

Management and Survival of Pleural Mesothelioma: A Record Linkage Study

Management and Survival of Pleural Mesothelioma: A Record Linkage Study

Calretinin as a blood-based biomarker for mesothelioma

Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis

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