A Diagnostic Assay Based on MicroRNA Expression Accurately Identifies Malignant Pleural Mesothelioma
The definitive identification of malignant pleural mesothelioma (MPM) has significant clinical implications, yet other malignancies often involve the lung pleura, confounding the diagnosis of MPM. In the absence of accurate markers, MPM can be difficult to distinguish from peripheral lung adenocarci...
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| Veröffentlicht in: | The Journal of molecular diagnostics : JMD 2010-11, Vol.12 (6), p.771-779 |
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| creator | Benjamin, Hila Lebanony, Danit Rosenwald, Shai Cohen, Lahav Gibori, Hadas Barabash, Naama Ashkenazi, Karin Goren, Eran Meiri, Eti Morgenstern, Sara Perelman, Marina Barshack, Iris Goren, Yaron Edmonston, Tina Bocker Chajut, Ayelet Aharonov, Ranit Bentwich, Zvi Rosenfeld, Nitzan Cohen, Dalia |
| description | The definitive identification of malignant pleural mesothelioma (MPM) has significant clinical implications, yet other malignancies often involve the lung pleura, confounding the diagnosis of MPM. In the absence of accurate markers, MPM can be difficult to distinguish from peripheral lung adenocarcinoma and metastatic epithelial cancers. MicroRNA expression is tissue-specific and highly informative for identifying tumor origin. We identified microRNA biomarkers for the differential diagnosis of MPM and developed a standardized microRNA-based assay. Formalin-fixed, paraffin-embedded samples of 33 MPM and 210 carcinomas were used for assay development. Using microarrays, we identified microRNAs differentially expressed between MPM and various carcinomas. Hsa-miR-193–3p was overexpressed in MPM, while hsa-miR-200c and hsa-miR-192 were overexpressed in peripheral lung adenocarcinoma and carcinomas that frequently metastasize to lung pleura. We developed a standardized diagnostic assay based on the expression of these microRNAs. The assay reached a sensitivity of 100% and a specificity of 94% in a blinded validation set of 68 samples from the lung and pleura. This diagnostic assay can provide a useful tool in the differential diagnosis of MPM from other malignancies in the pleura. |
| doi_str_mv | 10.2353/jmoldx.2010.090169 |
| format | Article |
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In the absence of accurate markers, MPM can be difficult to distinguish from peripheral lung adenocarcinoma and metastatic epithelial cancers. MicroRNA expression is tissue-specific and highly informative for identifying tumor origin. We identified microRNA biomarkers for the differential diagnosis of MPM and developed a standardized microRNA-based assay. Formalin-fixed, paraffin-embedded samples of 33 MPM and 210 carcinomas were used for assay development. Using microarrays, we identified microRNAs differentially expressed between MPM and various carcinomas. Hsa-miR-193–3p was overexpressed in MPM, while hsa-miR-200c and hsa-miR-192 were overexpressed in peripheral lung adenocarcinoma and carcinomas that frequently metastasize to lung pleura. We developed a standardized diagnostic assay based on the expression of these microRNAs. The assay reached a sensitivity of 100% and a specificity of 94% in a blinded validation set of 68 samples from the lung and pleura. This diagnostic assay can provide a useful tool in the differential diagnosis of MPM from other malignancies in the pleura.</description><identifier>ISSN: 1525-1578</identifier><identifier>EISSN: 1943-7811</identifier><identifier>DOI: 10.2353/jmoldx.2010.090169</identifier><identifier>PMID: 20864637</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Biomarkers, Tumor - genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma - diagnosis ; Mesothelioma - genetics ; Mesothelioma - pathology ; Microarray Analysis - methods ; Microarray Analysis - standards ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Pathology ; Pleural Neoplasms - diagnosis ; Pleural Neoplasms - genetics ; Pleural Neoplasms - pathology ; Regular ; Sensitivity and Specificity</subject><ispartof>The Journal of molecular diagnostics : JMD, 2010-11, Vol.12 (6), p.771-779</ispartof><rights>American Society for Investigative Pathology and Association for Molecular Pathology</rights><rights>2010 American Society for Investigative Pathology and Association for Molecular Pathology</rights><rights>2010 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved. 2010 American Society for Investigative Pathology and Association for Molecular Pathology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c575t-d5000806f0f084d1c2ab15ff1b57da8f0000f0d73fa49986b4a6e90cdcbe12e53</citedby><cites>FETCH-LOGICAL-c575t-d5000806f0f084d1c2ab15ff1b57da8f0000f0d73fa49986b4a6e90cdcbe12e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1525157810601274$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20864637$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Benjamin, Hila</creatorcontrib><creatorcontrib>Lebanony, Danit</creatorcontrib><creatorcontrib>Rosenwald, Shai</creatorcontrib><creatorcontrib>Cohen, Lahav</creatorcontrib><creatorcontrib>Gibori, Hadas</creatorcontrib><creatorcontrib>Barabash, Naama</creatorcontrib><creatorcontrib>Ashkenazi, Karin</creatorcontrib><creatorcontrib>Goren, Eran</creatorcontrib><creatorcontrib>Meiri, Eti</creatorcontrib><creatorcontrib>Morgenstern, Sara</creatorcontrib><creatorcontrib>Perelman, Marina</creatorcontrib><creatorcontrib>Barshack, Iris</creatorcontrib><creatorcontrib>Goren, Yaron</creatorcontrib><creatorcontrib>Edmonston, Tina Bocker</creatorcontrib><creatorcontrib>Chajut, Ayelet</creatorcontrib><creatorcontrib>Aharonov, Ranit</creatorcontrib><creatorcontrib>Bentwich, Zvi</creatorcontrib><creatorcontrib>Rosenfeld, Nitzan</creatorcontrib><creatorcontrib>Cohen, Dalia</creatorcontrib><title>A Diagnostic Assay Based on MicroRNA Expression Accurately Identifies Malignant Pleural Mesothelioma</title><title>The Journal of molecular diagnostics : JMD</title><addtitle>J Mol Diagn</addtitle><description>The definitive identification of malignant pleural mesothelioma (MPM) has significant clinical implications, yet other malignancies often involve the lung pleura, confounding the diagnosis of MPM. 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This diagnostic assay can provide a useful tool in the differential diagnosis of MPM from other malignancies in the pleura.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Mesothelioma - diagnosis</subject><subject>Mesothelioma - genetics</subject><subject>Mesothelioma - pathology</subject><subject>Microarray Analysis - methods</subject><subject>Microarray Analysis - standards</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Pathology</subject><subject>Pleural Neoplasms - diagnosis</subject><subject>Pleural Neoplasms - genetics</subject><subject>Pleural Neoplasms - pathology</subject><subject>Regular</subject><subject>Sensitivity and Specificity</subject><issn>1525-1578</issn><issn>1943-7811</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uk1v1DAQjRCIfsAf4IB845RiO3E-JFQptAUqdQHxcbYce7L14tiLJ6m6_x6vUiraAydb8968eZo3WfaK0RNeiOLtZgzO3J5wmgq0paxqn2SHrC2LvG4Ye5r-goucibo5yI4QN5Sysqz48-yA06Yqq6I-zExHzq1a-4CT1aRDVDvyXiEYEjxZWR3Dt88dubjdRkC0qdZpPUc1gduRSwN-soMFJCvl7NorP5GvDhLuyAowTNfgbBjVi-zZoBzCy7v3OPv54eLH2af86svHy7PuKteiFlNuBKW0odVAB9qUhmmueiaGgfWiNqoZEpoQUxeDKtu2qfpSVdBSbXQPjIMojrPTRXc79yMYnewlK3Ib7ajiTgZl5UPE22u5DjeSt1XRMpYE3twJxPB7BpzkaFGDc8pDmFHWohW8YE2dmHxhpg0hRhjupzAq9-nIJR25T0cu6aSm1__6u2_5G0civFsIkLZ0YyFK1Ba8BmMj6EmaYP-vf_qoXTvrrVbuF-wAN2GOPu1fMolcUvl9fx_782C0oozXZfEHffC4Cg</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Benjamin, Hila</creator><creator>Lebanony, Danit</creator><creator>Rosenwald, Shai</creator><creator>Cohen, Lahav</creator><creator>Gibori, Hadas</creator><creator>Barabash, Naama</creator><creator>Ashkenazi, Karin</creator><creator>Goren, Eran</creator><creator>Meiri, Eti</creator><creator>Morgenstern, Sara</creator><creator>Perelman, Marina</creator><creator>Barshack, Iris</creator><creator>Goren, Yaron</creator><creator>Edmonston, Tina Bocker</creator><creator>Chajut, Ayelet</creator><creator>Aharonov, Ranit</creator><creator>Bentwich, Zvi</creator><creator>Rosenfeld, Nitzan</creator><creator>Cohen, Dalia</creator><general>Elsevier Inc</general><general>American Society for Investigative Pathology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20101101</creationdate><title>A Diagnostic Assay Based on MicroRNA Expression Accurately Identifies Malignant Pleural Mesothelioma</title><author>Benjamin, Hila ; 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This diagnostic assay can provide a useful tool in the differential diagnosis of MPM from other malignancies in the pleura.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20864637</pmid><doi>10.2353/jmoldx.2010.090169</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarkers, Tumor - genetics Gene Expression Regulation, Neoplastic Humans Mesothelioma - diagnosis Mesothelioma - genetics Mesothelioma - pathology Microarray Analysis - methods Microarray Analysis - standards MicroRNAs - genetics MicroRNAs - metabolism Pathology Pleural Neoplasms - diagnosis Pleural Neoplasms - genetics Pleural Neoplasms - pathology Regular Sensitivity and Specificity |
| title | A Diagnostic Assay Based on MicroRNA Expression Accurately Identifies Malignant Pleural Mesothelioma |
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