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Recent Advances in Diagnosis of Malignant Mesothelioma
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Recent Advances in Diagnosis of Malignant Mesothelioma

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 18644

Special Issue Editor

Dr. Greta Alì

E-Mail Website
Guest Editor
Anatomic Pathology Section, Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
Interests: lung cancer; malignant pleural mesothelioma; molecular pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in the diagnosis, characterization, and therapy of many malignancies have significantly improved the survival of patients with cancer. However, for some hematological and solid malignancies, including mesothelioma, although there have been increases in our knowledge of the main causes, and improvements in clinical management, the overall survival is still short. Malignant mesothelioma is one of the most malignant tumors, fortunately relatively rare, and mainly associated with asbestos exposure. It was demonstrated that early diagnosis significantly improves overall survival. Unfortunately, malignant mesothelioma is mostly diagnosed at an advanced stage, when it is untreatable with the available therapeutic strategies. Mesothelioma is a complex and heterogeneous disease and the search for mesothelioma biomarkers has been ongoing for the last 30 years. In fact, tumor biomarkers can play an important role not only in the screening (for the early detection of disease), diagnosis, and prognosis, but also in the predictive and monitoring treatment response. However, currently, the diagnostic biomarkers are characterized by their relatively poor sensitivity and specificity for malignant mesothelioma.

Multidisciplinary approaches have made a difference in the diagnosis of the disease. Radiologic imaging is critical to the diagnosis of patients with malignant mesothelioma. Thoracentesis and cytological and, more often, pleural biopsy are required in the majority of cases for accurate diagnosis and histologic subtyping.

For this Special Issue, entitled “Recent Advances in Diagnosis of Malignant Mesothelioma”, we propose to address the current diagnostic approaches and novel or established biomarkers that can be used not only for the diagnosis, but also the prognosis of disease and individual responses to therapies. 

Dr. Greta Alì
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Malignant mesotelioma
  • Pleural malignancy
  • Imaging modalities
  • Staging
  • Cytology
  • Tissue
  • Pleural biopsy
  • Diagnostic
  • Prognosis
  • Pathology
  • Biomarker
  • Immunohistochemistry

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Published Papers (6 papers)

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Research

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20 pages, 2952 KiB  
Article
Diagnostics of BAP1-Tumor Predisposition Syndrome by a Multitesting Approach: A Ten-Year-Long Experience
by Marika Sculco, Marta La Vecchia, Anna Aspesi, Michela Giulia Clavenna, Michela Salvo, Giulia Borgonovi, Alessandra Pittaro, Gianluca Witel, Francesca Napoli, Angela Listì, Federica Grosso, Roberta Libener, Antonio Maconi, Ottavio Rena, Renzo Boldorini, Daniela Giachino, Paolo Bironzo, Antonella Maffè, Greta Alì, Lisa Elefanti, Chiara Menin, Luisella Righi, Cristian Tampieri, Giorgio Vittorio Scagliotti, Caterina Dianzani, Daniela Ferrante, Enrica Migliore, Corrado Magnani, Dario Mirabelli, Giuseppe Matullo and Irma Dianzaniadd Show full author list remove Hide full author list
Diagnostics 2022, 12(7), 1710; https://doi.org/10.3390/diagnostics12071710 - 13 Jul 2022
Cited by 8 | Viewed by 3065
Abstract
Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the [...] Read more.
Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of BAP1-TPDS, along with a clinical update and cascade genetic testing of previously reported BAP1-TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected BAP1-TPDS and validated pathogenic variants (PVs) by assessing BAP1 somatic loss in matching tumor specimens. Overall, we identified seven patients (7/101, 6.9%) carrying six different germline BAP1 PVs, including one novel variant. Consistently, cascade testing revealed a total of seven BAP1 PV carriers. In addition, we explored the mutational burden of BAP1-TPDS tumors by targeted next-generation sequencing. Lastly, we found that certain tumors present in PV carriers retain a wild-type BAP1 allele, suggesting a sporadic origin of these tumors or a functional role of heterozygous BAP1 in neoplastic development. Altogether, our findings have important clinical implications for therapeutic response of BAP1-TPDS patients. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis of Malignant Mesothelioma)
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12 pages, 45825 KiB  
Article
Gene Expression Analysis of Biphasic Pleural Mesothelioma: New Potential Diagnostic and Prognostic Markers
by Rossella Bruno, Anello Marcello Poma, Greta Alì, Claudia Distefano, Agnese Proietti, Antonio Chella, Marco Lucchi, Franca Melfi, Renato Franco and Gabriella Fontanini
Diagnostics 2022, 12(3), 674; https://doi.org/10.3390/diagnostics12030674 - 10 Mar 2022
Cited by 2 | Viewed by 2627
Abstract
Biphasic is the second most common histotype of pleural mesothelioma (PM). It shares epithelioid and sarcomatoid features and is challenging to diagnose. The aim of this study was to identify biphasic PM markers to improve subtyping and prognosis definition. The expression levels of [...] Read more.
Biphasic is the second most common histotype of pleural mesothelioma (PM). It shares epithelioid and sarcomatoid features and is challenging to diagnose. The aim of this study was to identify biphasic PM markers to improve subtyping and prognosis definition. The expression levels of 117 cancer genes, evaluated using the nanoString system, were compared between the three major histotypes (epithelioid, sarcomatoid, and biphasic), and expression differences within biphasic PM were evaluated in relation to the percentage of epithelioid components. Biphasic PM overexpressed CTNNA1 and TIMP3 in comparison to sarcomatoid, and COL16A1 and SDC1 in comparison to epithelioid PM. CFB, MSLN, CLDN15, SERPINE1, and PAK4 were deregulated among all histotypes, leading to the hypothesis of a gradual expression from epithelioid to sarcomatoid PM. According to gene expression, biphasic PM samples were divided in two clusters with a significant difference in the epithelioid component. ADCY4, COL1A1, and COL4A2 were overexpressed in the biphasic group with a low percentage of epithelioid component. Survival analysis using TCGA data showed that high COL1A1 and COL4A2 expression levels correlate with poor survival in PM patients. Herein, we identified markers with the potential to improve diagnosis and prognostic stratification of biphasic PM, which is still an orphan tumor. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis of Malignant Mesothelioma)
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10 pages, 739 KiB  
Article
Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?
by Rudy Foddis, Maria Franzini, Alessandra Bonotti, Riccardo Marino, Roberto Silvestri, Poupak Fallahi, Dante Chiappino, Michele Emdin, Aldo Paolicchi and Alfonso Cristaudo
Diagnostics 2022, 12(2), 311; https://doi.org/10.3390/diagnostics12020311 - 26 Jan 2022
Cited by 5 | Viewed by 2187
Abstract
Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum [...] Read more.
Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582–0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807–0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis of Malignant Mesothelioma)
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8 pages, 992 KiB  
Article
Assessment of Glutathione Peroxidase-1 (GPX1) Gene Expression as a Specific Diagnostic and Prognostic Biomarker in Malignant Pleural Mesothelioma
by Amal F. Gharib, Muhammad Alaa Eldeen, Amany Salah Khalifa, Wael H. Elsawy, Emad Mohamed Eed, Ahmad El Askary, Refaat A. Eid, Mohamed A. Soltan and Nermin Raafat
Diagnostics 2021, 11(12), 2285; https://doi.org/10.3390/diagnostics11122285 - 7 Dec 2021
Cited by 11 | Viewed by 2784
Abstract
Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of [...] Read more.
Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of MPM are considered the cornerstone success factors for the management of early MPM. Glutathione peroxidase-1 (GPX1) is an intracellular protein found to be extensively distributed in all cells, and it belongs to the GPX group. In the current study, we included ninety-eight patients with MPM that underwent surgery at the Zagazig University Hospital in Egypt. We assessed GPX1 gene expression level as it was thought to be related to pathogenicity of cancer in a variety of malignant tumors. We observed a significant elevation in GPX1-mRNA levels in MPM relative to the nearby normal pleural tissues. It was found to be of important diagnostic specificity in the differentiation of MPM from normal tissues. Moreover, we studied the survival of patients in correlation to the GPX1 expression levels and we reported that median overall survival was about 16 months in patients with high GPX1 expression levels, while it was found to be about 40 months in low GPX1 levels. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis of Malignant Mesothelioma)
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Review

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14 pages, 4189 KiB  
Review
The Use of Chest Magnetic Resonance Imaging in Malignant Pleural Mesothelioma Diagnosis
by Federica Volpi, Caterina A. D’Amore, Leonardo Colligiani, Alessio Milazzo, Silvia Cavaliere, Annalisa De Liperi, Emanuele Neri and Chiara Romei
Diagnostics 2022, 12(3), 750; https://doi.org/10.3390/diagnostics12030750 - 19 Mar 2022
Cited by 3 | Viewed by 4760
Abstract
In recent years, many articles have demonstrated that magnetic resonance imaging (MRI) may be performed successfully in the study of the chest. The aim of this study was to evaluate the potential role of MRI in the differentiation of benign from malignant pleural [...] Read more.
In recent years, many articles have demonstrated that magnetic resonance imaging (MRI) may be performed successfully in the study of the chest. The aim of this study was to evaluate the potential role of MRI in the differentiation of benign from malignant pleural disease with a special focus on malignant pleural mesothelioma and on MRI protocols. A systematic literature search was performed to find original articles about chest MRI in patients with either benign or malignant pleural disease. We retrieved 1246 papers and 17 studies were finally identified as being in accordance with our purpose. For a morphologic assessment, T1-weighted and T2-weighted sequences were usually performed, eventually associated with T1 post-contrast sequences for better detection of pleural lesions. Functional sequences such as Diffusion Weighting Imaging (DWI), associated with the evaluation of Apparent Diffusion Coefficient (ADC) maps, were lately and gradually introduced in chest MRI protocols and their potentiality in differentiating benign from malignant disease has been investigated by many authors. Many progresses have been performed to improve quality images and diagnostic performances of MRI. A better and early identification of pleural disease may be obtained, providing MRI as a possible tool that can differentiate malignant from benign pleural disease without using invasive procedures. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis of Malignant Mesothelioma)
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Other

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8 pages, 8667 KiB  
Brief Report
Unusual Histology in Mesothelioma: A Report of Two Cases with a Brief Review
by Francesca Bono, Stefano Ceola, Carlo Beretta and Marta Jaconi
Diagnostics 2022, 12(2), 371; https://doi.org/10.3390/diagnostics12020371 - 1 Feb 2022
Cited by 3 | Viewed by 2147
Abstract
Mesothelioma is often difficult to diagnose due to its rarity and its unusual histopathological features that could lend to diagnostic pitfalls and misdiagnosis. The WHO histological classification of pleural tumors in 2021 recommended a pathologic grading system for malignant pleural mesothelioma. Architectural aspects [...] Read more.
Mesothelioma is often difficult to diagnose due to its rarity and its unusual histopathological features that could lend to diagnostic pitfalls and misdiagnosis. The WHO histological classification of pleural tumors in 2021 recommended a pathologic grading system for malignant pleural mesothelioma. Architectural aspects and cytological features, with nuclear grading, bent on a neoplastic score with fundamental prognostic and diagnostic value. Unusual features must be correctly assigned in the grading system to avoid misdiagnosis, especially toward metastatic lesions or reactive pleural processes. In this paper, we present two cases as examples of unusual morphological and architectural features with a brief literature review. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis of Malignant Mesothelioma)
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