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Application of immunohistochemistry in diagnosis and management of malignant mesothelioma.

ABSTRACT: Immunohistochemistry plays an indispensable role in accurate diagnosis of malignant mesothelioma, particularly in morphologically challenging cases and in biopsy and cytology specimens, where tumor architecture is difficult or impossible to evaluate. Application of a targeted panel of mesothelial- and epithelial-specific markers permits correct identification of tumor lineage in the vast majority of cases. An immunopanel including two mesothelial markers (calretinin, CK5/6, WT-1, or D2-40) and two epithelial markers (MOC-31 and claudin-4) offers good sensitivity and specificity, with adjustments as appropriate for the differential diagnosis. Once mesothelial lineage is established, malignancy-specific studies can help verify a diagnosis of malignant mesothelioma. BAP1 loss, CDKN2A homozygous deletion, and MTAP loss are highly specific markers of malignancy in a mesothelial lesion, and they attain acceptable diagnostic sensitivity when applied as a diagnostic panel. Novel markers of malignancy, such as 5-hmC loss and increased EZH2 expression, are promising, but have not yet achieved widespread clinical adoption. Some diagnostic markers also have prognostic significance, and PD-L1 immunohistochemistry may predict tumor response to immunotherapy. Application and interpretation of these immnuomarkers should always be guided by clinical history, radiographic findings, and above all histomorphology.

SUBMITTER: Chapel DB

PROVIDER: S-EPMC7082260 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Application of immunohistochemistry in diagnosis and management of malignant mesothelioma.

Chapel David B DB Schulte Jefree J JJ Husain Aliya N AN Krausz Thomas T

Translational lung cancer research 20200201 Suppl 1

Immunohistochemistry plays an indispensable role in accurate diagnosis of malignant mesothelioma, particularly in morphologically challenging cases and in biopsy and cytology specimens, where tumor architecture is difficult or impossible to evaluate. Application of a targeted panel of mesothelial- and epithelial-specific markers permits correct identification of tumor lineage in the vast majority of cases. An immunopanel including two mesothelial markers (calretinin, CK5/6, WT-1, or D2-40) and t ...[more]

PMID: 32206567

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Project description:BackgroundIn order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002.MethodsBasic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated.Results49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM.With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia.In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers.The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3).46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out.ConclusionsIn order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.

Project description:Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis per se is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.

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Application of immunohistochemistry in diagnosis and management of malignant mesothelioma.

Publications

Application of immunohistochemistry in diagnosis and management of malignant mesothelioma.

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