{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:09:04Z","timestamp":1792807744530,"version":"4.5.0"},"reference-count":73,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Respir Dis"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p> The use of biomarkers on pleural fluid (PF) specimens may assist the decision-making process and enhance clinical diagnostic pathways. Three paradigmatic examples are heart failure, tuberculosis and, particularly, malignancy. An elevated PF concentration of the amino-terminal fragment of probrain natriuretic peptide (&gt;1500\u2009pg\/ml) is a hallmark of acute decompensated heart failure. Adenosine deaminase, interferon-\u03b3 and interleukin-27 are three valuable biomarkers for diagnosing tuberculous pleurisy, yet only the first has been firmly established in clinical practice. Diagnostic PF biomarkers for malignancy can be classified as soluble-protein based, immunocytochemical and nucleic-acid based. Soluble markers (e.g. carcinoembryonic antigen (CEA), carbohydrate antigen 15\u20133, mesothelin) are only indicative of cancer, but not confirmatory. Immunocytochemical studies on PF cell blocks allow: (a) to distinguish mesothelioma from reactive mesothelial proliferations (e.g. loss of BAP1 nuclear expression, complemented by the demonstration of p16 deletion using fluorescence in situ hybridization, indicate mesothelioma); (b) to separate mesothelioma from adenocarcinoma (e.g. calretinin, CK 5\/6, WT-1 and D2-40 are markers of mesothelioma, whereas CEA, EPCAM, TTF-1, napsin A, and claudin 4 are markers of carcinoma); and (c) to reveal tumor origin in pleural metastases of an unknown primary site (e.g. TTF-1 and napsin A for lung adenocarcinoma, p40 for squamous lung cancer, GATA3 and mammaglobin for breast cancer, or synaptophysin and chromogranin A for neuroendocrine tumors). Finally, PF may provide an adequate sample for analysis of molecular markers to guide patients with non-small cell lung cancer to appropriate targeted therapies. Molecular testing must include, at least, mutations of epidermal growth-factor receptor and BRAF V600E, translocations of rat osteosarcoma and anaplastic lymphoma kinase, and expression of programmed death ligand 1. <\/jats:p>","DOI":"10.1177\/1753466618808660","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T07:22:37Z","timestamp":1540452157000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":103,"title":["Biomarkers in the diagnosis of pleural diseases: a 2018 update"],"prefix":"10.1177","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-8061","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Porcel","sequence":"first","affiliation":[{"name":"Pleural Medicine Unit, Department of Internal Medicine, Arnau de Vilanova University Hospital, Avda Alcalde Rovira Roure 80, 25198 Lleida, 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