The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review

Alì, Greta; Bruno, Rossella; Fontanini, Gabriella

doi:10.21037/jtd.2017.10.125

Cited by 45 publications

(45 citation statements)

References 61 publications

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“…The epithelioid subtype is the most common (60–80%) and has the best prognosis with an OS of 13.1 months. The sarcomatoid subtype, on the other hand, has the worst prognosis with an OS of 4–6 months [60]. MPE occurs in 54–90% of all malignant pleural mesothelioma cases and forms at an early stage [21,61,62].…”

Section: Cancer and Malignant Pleural Effusionmentioning

confidence: 99%

Malignant Pleural Effusion and Its Current Management: A Review

et al. 2019

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Malignant pleural effusion (MPE) is an exudative effusion with malignant cells. MPE is a common symptom and accompanying manifestation of metastatic disease. It affects up to 15% of all patients with cancer and is the most common in lung, breast cancer, lymphoma, gynecological malignancies and malignant mesothelioma. In the last year, many studies were performed focusing on the pathophysiological mechanisms of MPE. With the advancement in molecular techniques, the importance of tumor-host cell interactions is becoming more apparent. Additionally, the process of pathogenesis is greatly affected by activating mutations of EGFR, KRAS, PIK3CA, BRAF, MET, EML4/ALK and RET, which correlate with an increased incidence of MPE. Considering all these changes, the authors aim to present a literature review of the newest findings, review of the guidelines and pathophysiological novelties in this field. Review of the just recently, after seven years published, practice guidelines, as well as analysis of more than 70 articles from the Pubmed, Medline databases that were almost exclusively published in indexed journals in the last few years, have relevance and contribute to the better understanding of the presented topic. MPE still presents a severe medical condition in patients with advanced malignancy. Recent findings in the field of pathophysiological mechanisms of MPE emphasize the role of molecular factors and mutations in the dynamics of the disease and its prognosis. Treatment guidelines offer a patient-centric approach with the use of new scoring systems, an out of hospital approach and ultrasound. The current guidelines address multiple areas of interest bring novelties in the form of validated prediction tools and can, based on evidence, improve patient outcomes. However, the role of biomarkers in a clinical setting, possible new treatment modalities and certain specific situations still present a challenge for new research.

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Section: Cancer and Malignant Pleural Effusionmentioning

confidence: 99%

Malignant Pleural Effusion and Its Current Management: A Review

et al. 2019

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“…Global incidence of MPM has risen steadily over the past decade, and it is predicted to reach the highest peak in 2020 (1,2). MPM is a heterogeneous tumor, including three main histological subtypes: Epithelioid (60-80%), sarcomatoid (<10%) and mixed (10-15%) (3,4).…”

Section: Introductionmentioning

confidence: 99%

“…Particularly, the differential diagnosis of MPM and benign pleural lesions is a hard task to accomplish, and currently the only criterion to certainly determine the malignancy is the presence of stromal or lung invasion (5). However, it is not always possible to estimate whether stromal invasion is present or not, according to quantitative and qualitative parameters of pleural biopsies and their representativeness of the whole lesion (4). Moreover, for many patients pleural biopsies are not available and diagnosis has to be made on cytological specimens from pleural effusions, whose diagnostic sensitivity is variable ranging from 20 to 70% (6).…”

Section: Introductionmentioning

confidence: 99%

A gene‑expression‑based test can outperform bap1 and p16 analyses in the differential diagnosis of pleural mesothelial proliferations

et al. 2019

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The demonstration of tissue invasion by histology is an essential criterion for the differential diagnosis of benign and malignant mesothelial proliferations. When tissue invasion cannot be identified, the use of ancillary tests is sometimes necessary. Among investigated markers, the loss of BRCA1 associated protein 1 (BAP1) protein expression and the homozygous deletion of p16 have shown 100% specificity in separating benign and malignant mesothelial lesions. However, beyond the excellent specificity of these two markers, their low sensitivity limits their clinical utility. In this context, a previous study developed and tested a novel tool for use in the differential diagnosis of malignant pleural mesothelioma (MPM) using the NanoString System and a classification algorithm. In the current study, the performance of gene classifiers were compared using BAP1 and p16 testing. p16 FISH and BAP1 immunohistochemistry were performed on the same series of 34 epithelioid MPM and 20 benign pleural lesions, which were previously analyzed by the system. The diagnostic performance of p16, BAP1 and our classification models were compared using ROC analysis. It was observed that BAP1 loss and p16 deletion were highly specific for MPM, since they were not detected in benign lesions. However, their AUC values were not completely satisfying (BAP1: 0.8235; p16: 0.7647) particularly due to their low sensitivities. As expected, combining BAP1 and p16 tests increased the diagnostic sensitivity, thus improving the AUC (0.8824). In the same series of cases, our MPM tool outperformed BAP1 and p16 tests using the 22 and 40-gene classification models (AUC 22-gene model: 0.9996; AUC 40-gene model: 0.9990). In conclusion, the present gene-expression-based classification exhibited great potential and further validation is required to support these findings in a prospective fashion, in order to provide a solid alternative for pleural proliferation diagnosis.

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“…Malignant mesothelioma is a fatal tumor caused by exposure to asbestos 13 . The absence of mesothelioma-specific markers has often made it difficult to diagnose malignant mesothelioma 14 . In our previous study 15 , we identified the sialylated protein HEG homolog 1 (HEG1) as a novel and precise mesothelioma marker.…”

Section: Introductionmentioning

confidence: 99%

Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1

Matsuura

Kaji

Tomioka

et al. 2018

Sci Rep

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The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1). HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma. SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma. In the present study, we investigated the epitope of SKM9-2. We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins. The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1. An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition. Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900. Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification. The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.

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The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review

Cited by 45 publications

References 61 publications

Malignant Pleural Effusion and Its Current Management: A Review

Malignant Pleural Effusion and Its Current Management: A Review

A gene‑expression‑based test can outperform bap1 and p16 analyses in the differential diagnosis of pleural mesothelial proliferations

Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1

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