Immunohistochemistry and Molecular Diagnostics of Pleural Malignant Mesothelioma

Betta, Pier-Giacomo; Magnani, Corrado; Bensi, T.; Trincheri, Nicol F.; Orecchia, Sara

doi:10.5858/arpa.2010-0604-ra

Cited by 43 publications

(39 citation statements)

References 54 publications

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Section: Introductionmentioning

confidence: 99%

“…MPMs, particularly of the epithelioid subtype, may be hard to differentiate from adenocarcinoma arising in the lung periphery, and epidemiological evidence indicates that asbestos and smoking are shared risk factors for these diseases (2,13,14). Currently, the differential diagnosis of MM is based on a range of morphological analyses, including a combination of histological and immunohistochemical staining, and electron microscopy (13,15,16).Cytogenetic studies have been performed on MPMs and adenocarcinomas arising in the lung periphery, however, no chromosomal aberrations specific to either of the tumor types have been identified (2,14).Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a method for evaluating DNA copy number DNA copy number gains in malignant pleural mesothelioma …”

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confidence: 99%

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DNA copy number gains in malignant pleural mesothelioma

et al. 2015

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Abstract. Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an extremely poor prognosis. The incidence of MPM is increasing as a result of widespread exposure to asbestos. The molecular pathogenesis of MPM remains unclear. The present study analyzed the frequency of various genomic copy number gains (CNGs) in MPM using reverse transcription-quantitative polymerase chain reaction. A total of 83 primary MPMs and 53 primary lung adenocarcinomas were analyzed to compare the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2. In MPM, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 12 (14.5%), 8 (9.6%), 5 (6.0%), 4 (4.8%) and 1 (1.2%) of the samples, respectively. In lung adenocarcinomas, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%) of the samples, respectively. The CNGs of EGFR, KRAS and FGFR1 were significantly less frequent in the MPMs compared with the lung adenocarcinomas (P=0.0018, 0.048 and 0.018, respectively). Overall, the MPMs exhibited these CNGs less frequently compared with the lung adenocarcinomas (P=0.0002). The differences in CNGs between the two tumor types suggested that they are genetically different. IntroductionMalignant pleural mesothelioma (MPM) is a tumor derived from the mesothelial cells lining the pleural spaces. MPM has highly invasive and aggressive clinical characteristics. Approximately 80% of MPM patients have a history of occupational asbestos exposure, which is considered to be a risk factor for the development of the disease (1). The molecular pathogenesis of MPM is not well understood. The most common mutations in MPMs are losses in 9p21, 1p36, 14q32 and 22q12, and gains in 5p, 7p and 8q24, which have been detected by comparative genomic hybridization analysis (2,3). Homozygous deletion of the 9p21 locus encoding two critical cyclin-dependent kinase inhibitors, p16INK4a and p15 INK4b , have been reported in up to 80% of MPMs, and this mutation may be of diagnostic utility (4,5). The tumor suppressor neurofibromin 2 is encoded by the NF2 gene, located on chromosome 22q12. Mutations in NF2 are found in ~40% of MPMs, and heterozygous loss of NF2 is identified in ~74% of MPMs (6,7). Mutations are rare in the TP53 and RAS genes, which are frequently present in epithelial solid tumors (8,9). Epigenetic alterations, such as DNA methylation, have been found in MPMs, which have a different profile compared with lung cancer (10-12). MPMs, particularly of the epithelioid subtype, may be hard to differentiate from adenocarcinoma arising in the lung periphery, and epidemiological evidence indicates that asbestos and smoking are shared risk factors for these diseases (2,13,14). Currently, the differential diagnosis of MM is based on a range of morphological analyses, including a combination of histological and immunohistochemical staining, and electron microscopy (13,15,16).Cytogenetic studies have been performed on MPMs and adenocarcinomas arising in the lung periphery, however, no chromosomal aberra...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

DNA copy number gains in malignant pleural mesothelioma

et al. 2015

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“…The exact combination and number of antigens to evaluate is dependent on the histopathological patterns of MPM (epithelioid/sarcomatoid), the diagnostic dilemma to be resolved, and on the antibodies available in the pathology laboratory (45,46). Since none of the antibodies used for the diagnosis of MPM is 100% sensitive or specific, the International Mesothelioma Interest Group (IMIG) recommends an initial workup with an immunohistochemical panel comprising pancytokeratin (multiple keratins, such as AE1/AE3, CAM5.2) plus two mesothelial markers and two markers for the other tumor under consideration based on morphology.…”

Section: Immunohistochemical Markers For the Diagnosis Of Mpmmentioning

confidence: 99%

“…The most useful general carcinoma markers are carcinoembryonic antigen (CEA), BerEP4, CD15 (LeuM1), MOC31, BG8, claudin 4, and B72.3 (24,33,45,46). Other immunohistochemical markers can be used to confirm the origin of carcinoma.…”

Section: Epithelioid/mixed Malignant Mesothelioma Versus Carcinomamentioning

confidence: 99%

“…The most useful markers for sarcomatoid MPM are calretinin and D2-40, which are expressed in a variable percentage of cases and which can recognize the mesothelial origin of the neoplasm (3,45). Most sarcomatoid/ desmoplastic MPMs are strongly positive for cytokeratins, whereas most sarcomas are keratin-negative.…”

Section: Sarcomatoid Malignant Mesothelioma Versus Spindle Cell Maligmentioning

confidence: 99%

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

Alì¹,

Bruno²,

Fontanini³

2018

J. Thorac. Dis.

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on the application of a panel including positive (mesothelial-related) and negative markers with greater than 80% sensitivity and specificity, which need to be selected based on morphology and clinical information.Moreover, in challenging cases, fluorescent in situ hybridization (FISH) testing for the p16 deletion and IHC to evaluate the loss of BRCA1-associated protein 1 (BAP1) expression could be useful in distinguishing benign from malignant pleural proliferations.

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