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In addition, immunohistochemistry allows for the evaluation of cellular localization of proteins in the context of tumor structure. In an era of precision medicine, pathologists are required to classify lung cancer into specific subtypes and assess biomarkers relevant to molecular-targeted therapies. This review summarizes the hot topics of immunohistochemistry in lung cancer, including (i) adenocarcinoma vs squamous cell carcinoma; (ii) neuroendocrine markers; (iii) ALK, ROS1, and EGFR; (iv) PD-L1 (CD274); (v) lung carcinoma vs malignant mesothelioma; and (vi) NUT carcinoma. Major pitfalls in evaluating immunohistochemical results are also described.<\/jats:p>","DOI":"10.3390\/cancers10030072","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T05:06:43Z","timestamp":1521090403000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Update on Immunohistochemistry for the Diagnosis of Lung Cancer"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6444-3861","authenticated-orcid":false,"given":"Kentaro","family":"Inamura","sequence":"first","affiliation":[{"name":"Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.5858\/arpa.2015-0535-SA","article-title":"Impact of recent developments in lung cancer on the practice of pathology","volume":"140","author":"Cagle","year":"2016","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Thunnissen, E., Allen, T.C., Adam, J., Aisner, D.L., Beasley, M.B., Borczuk, A.C., Cagle, P.T., Capelozzi, V.L., Cooper, W., and Hariri, L.P. (2018). Immunohistochemistry of pulmonary biomarkers: A perspective from members of the pulmonary pathology society. Arch. Pathol. Lab. Med., 142.","DOI":"10.5858\/arpa.2017-0106-SA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"570","DOI":"10.21037\/tlcr.2017.07.06","article-title":"Immunohistochemistry for predictive biomarkers in non-small cell lung cancer","volume":"6","year":"2017","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.5858\/arpa.2016-0550-RA","article-title":"Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms","volume":"141","author":"Woo","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1389450116666150330114441","article-title":"Does immunohistochemistry represent a robust alternative technique in determining drugable predictive gene alterations in non-small cell lung cancer?","volume":"18","author":"Rossi","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_6","unstructured":"Travis, W.D., Brambilla, E., Burke, A.P., Marx, A., and Nicholson, A.G. (2015). WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, International Agency for Research on Cancer (IARC). [4th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2014). Comprehensive molecular profiling of lung adenocarcinoma. Nature, 511, 543\u2013550.","DOI":"10.1038\/nature13385"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 489, 519\u2013525.","DOI":"10.1038\/nature11404"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature14664","article-title":"Comprehensive genomic profiles of small cell lung cancer","volume":"524","author":"George","year":"2015","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/ng.2396","article-title":"Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer","volume":"44","author":"Peifer","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/ng.2405","article-title":"Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer","volume":"44","author":"Rudin","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1126\/science.aaa1348","article-title":"Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer","volume":"348","author":"Rizvi","year":"2015","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.jtho.2016.01.010","article-title":"KRAS and NKX2-1 mutations in invasive mucinous adenocarcinoma of the lung","volume":"11","author":"Hwang","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Polley, E., Kunkel, M., Evans, D., Silvers, T., Delosh, R., Laudeman, J., Ogle, C., Reinhart, R., Selby, M., and Connelly, J. (2016). Small Cell Lung Cancer Screen of Oncology Drugs, Investigational Agents, and Gene and microRNA Expression. J. Natl. Cancer Inst., 108.","DOI":"10.1093\/jnci\/djw122"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00428-014-1535-4","article-title":"Prognostic and predictive biomarkers in lung cancer. A review","volume":"464","author":"Thunnissen","year":"2014","journal-title":"Virchows Arch."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sabir, S.R., Yeoh, S., Jackson, G., and Bayliss, R. (2017). EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients. Cancers, 9.","DOI":"10.3390\/cancers9090118"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Inamura, K. (2017). Diagnostic and Therapeutic Potential of MicroRNAs in Lung Cancer. Cancers, 9.","DOI":"10.3390\/cancers9050049"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/JTO.0b013e318206a221","article-title":"International association for the study of lung cancer\/american thoracic society\/european respiratory society international multidisciplinary classification of lung adenocarcinoma","volume":"6","author":"Travis","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fonc.2017.00193","article-title":"Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification","volume":"7","author":"Inamura","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/modpathol.2011.92","article-title":"Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens","volume":"24","author":"Rekhtman","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1097\/PAS.0000000000000439","article-title":"Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis","volume":"39","author":"Kadota","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.jtho.2016.01.020","article-title":"The Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs","volume":"11","author":"Micke","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/PAI.0b013e3181bdf4e7","article-title":"Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors","volume":"18","author":"Matoso","year":"2010","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/modpathol.3800422","article-title":"Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin","volume":"18","author":"Comperat","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1097\/PAS.0b013e3182498f2b","article-title":"A study of DeltaNp63 expression in lung non-small cell carcinomas","volume":"36","author":"Nonaka","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/modpathol.2011.173","article-title":"p40 (DeltaNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma","volume":"25","author":"Bishop","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1016\/j.ajpath.2015.08.018","article-title":"Insulinoma-Associated Protein 1 Is a Crucial Regulator of Neuroendocrine Differentiation in Lung Cancer","volume":"185","author":"Fujino","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ydbio.2015.10.009","article-title":"Insm1 controls the differentiation of pulmonary neuroendocrine cells by repressing Hes1","volume":"408","author":"Jia","year":"2015","journal-title":"Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15252","DOI":"10.1016\/S0021-9258(18)42173-4","article-title":"A novel human insulinoma-associated cDNA, IA-1, encodes a protein with \u201czinc-finger\u201d DNA-binding motifs","volume":"267","author":"Goto","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1097\/PAS.0000000000000916","article-title":"INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity","volume":"41","author":"Rooper","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/nrc3612","article-title":"Tyrosine kinase gene rearrangements in epithelial malignancies","volume":"13","author":"Shaw","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nature05945","article-title":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","volume":"448","author":"Soda","year":"2007","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/JTO.0b013e31815e8b60","article-title":"EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers","volume":"3","author":"Inamura","year":"2008","journal-title":"J. Thorac. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.1200\/JCO.2009.22.6993","article-title":"Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK","volume":"27","author":"Shaw","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/modpathol.2009.2","article-title":"EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset","volume":"22","author":"Inamura","year":"2009","journal-title":"Mod. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1056\/NEJMoa1006448","article-title":"Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer","volume":"363","author":"Kwak","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1056\/NEJMoa1311107","article-title":"Ceritinib in ALK-rearranged non-small-cell lung cancer","volume":"370","author":"Shaw","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1056\/NEJMoa1408440","article-title":"First-line crizotinib versus chemotherapy in ALK-positive lung cancer","volume":"371","author":"Solomon","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hofman, P. (2017). ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice. Cancers, 9.","DOI":"10.3390\/cancers9080107"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/JTO.0b013e318274a83e","article-title":"Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent","volume":"8","author":"Conklin","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1158\/1078-0432.CCR-16-1631","article-title":"Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non-Small Cell Lung Cancer","volume":"23","author":"Pelgrim","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.jtho.2017.01.020","article-title":"A sensitive ALK immunohistochemistry companion diagnostic test identifies patients eligible for treatment with Crizotinib","volume":"12","author":"Williams","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jtho.2015.12.111","article-title":"ALK Protein Analysis by IHC Staining after Recent Regulatory Changes: A Comparison of Two Widely Used Approaches, Revision of the Literature, and a New Testing Algorithm","volume":"11","author":"Marchetti","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/JTO.0000000000000115","article-title":"An international interpretation study using the ALK IHC antibody D5F3 and a sensitive detection kit demonstrates high concordance between ALK IHC and ALK FISH and between evaluators","volume":"9","author":"Wynes","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1200\/JCO.2011.35.6345","article-title":"ROS1 rearrangements define a unique molecular class of lung cancers","volume":"30","author":"Bergethon","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1158\/1078-0432.CCR-12-0550","article-title":"Identifying and targeting ROS1 gene fusions in non-small cell lung cancer","volume":"18","author":"Davies","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1056\/NEJMoa1406766","article-title":"Crizotinib in ROS1-rearranged non-small-cell lung cancer","volume":"371","author":"Shaw","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/modpathol.2013.192","article-title":"Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers","volume":"27","author":"Yoshida","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1200\/JCO.2016.71.3701","article-title":"Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement","volume":"35","author":"Lim","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cllc.2014.10.003","article-title":"ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer","volume":"16","author":"Boyle","year":"2015","journal-title":"Clin. Lung Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.lungcan.2013.11.019","article-title":"On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas","volume":"83","author":"Lantuejoul","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00428-016-2000-3","article-title":"Testing for ROS1 in non-small cell lung cancer: A review with recommendations","volume":"469","author":"Bubendorf","year":"2016","journal-title":"Virchows Arch."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1097\/PAS.0b013e3182960fa7","article-title":"ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas","volume":"37","author":"Sholl","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Cha, Y.J., Lee, J.S., Kim, H.R., Lim, S.M., Cho, B.C., Lee, C.Y., and Shim, H.S. (2014). Screening of ROS1 rearrangements in lung adenocarcinoma by immunohistochemistry and comparison with ALK rearrangements. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103333"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/jnci\/dji055","article-title":"Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers","volume":"97","author":"Shigematsu","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"66","DOI":"10.5858\/2008-0586-RAR1.1","article-title":"Is the epidermal growth factor receptor status in lung cancers reflected in clinicopathologic features?","volume":"134","author":"Inamura","year":"2010","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1200\/JCO.2014.57.3055","article-title":"Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists\/International Association for the study of lung cancer\/association for molecular pathology guideline","volume":"32","author":"Leighl","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1097\/JTO.0b013e318290868f","article-title":"Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology","volume":"8","author":"Lindeman","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1158\/1078-0432.CCR-08-2739","article-title":"Mutation-specific antibodies for the detection of EGFR mutations in non-small-cell lung cancer","volume":"15","author":"Yu","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/nature13954","article-title":"PD-1 blockade induces responses by inhibiting adaptive immune resistance","volume":"515","author":"Tumeh","year":"2014","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e1364828","DOI":"10.1080\/2162402X.2017.1364828","article-title":"PD-1 expression on tumor-specific T cells: Friend or foe for immunotherapy?","volume":"7","author":"Simon","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jtho.2016.04.014","article-title":"PD-L1 Expression in Lung Cancer","volume":"11","author":"Yu","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Schmidt, L.H., Kummel, A., Gorlich, D., Mohr, M., Brockling, S., Mikesch, J.H., Grunewald, I., Marra, A., Schultheis, A.M., and Wardelmann, E. (2015). PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136023"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.ejca.2014.01.018","article-title":"Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes","volume":"50","author":"Yang","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.lungcan.2015.05.007","article-title":"PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma","volume":"89","author":"Cooper","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14209","DOI":"10.18632\/oncotarget.3694","article-title":"The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs","volume":"6","author":"Tang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ejca.2015.12.033","article-title":"Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma","volume":"57","author":"Yang","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/JTO.0000000000000414","article-title":"Significance of programmed cell death-ligand 1 expression and its association with survival in patients with small cell lung cancer","volume":"10","author":"Ishii","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1002\/cam4.1172","article-title":"Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor","volume":"6","author":"Inamura","year":"2017","journal-title":"Cancer Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"18021","DOI":"10.18632\/oncotarget.14935","article-title":"High PD-L1 expression is associated with stage IV disease and poorer overall survival in 186 cases of small cell lung cancers","volume":"8","author":"Chang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa1504627","article-title":"Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer","volume":"373","author":"Brahmer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1200\/JCO.2017.74.3062","article-title":"Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057)","volume":"35","author":"Horn","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa1501824","article-title":"Pembrolizumab for the treatment of non-small-cell lung cancer","volume":"372","author":"Garon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1080\/14737159.2017.1398083","article-title":"PD-L1 immunohistochemistry for non-small cell lung carcinoma: Which strategy should be adopted?","volume":"17","author":"Hofman","year":"2017","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1200\/JCO.2013.51.4802","article-title":"Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma","volume":"31","author":"Weber","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.cllc.2016.03.003","article-title":"A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients with Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study","volume":"17","author":"Planchard","year":"2016","journal-title":"Clin. Lung Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/S1470-2045(16)30364-3","article-title":"Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: A multicentre, single-group, open-label, phase 2 trial","volume":"17","author":"Kaufman","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1056\/NEJMoa1709937","article-title":"Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer","volume":"377","author":"Antonia","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S1470-2045(17)30240-1","article-title":"Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): Dose-expansion cohort of a multicentre, open-label, phase 1b trial","volume":"18","author":"Gulley","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ilie, M., Khambata-Ford, S., Copie-Bergman, C., Huang, L., Juco, J., Hofman, V., and Hofman, P. (2017). Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186537"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jtho.2016.11.2228","article-title":"PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project","volume":"12","author":"Hirsch","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1001\/jamaoncol.2017.0013","article-title":"A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non-Small Cell Lung Cancer","volume":"3","author":"Rimm","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/modpathol.2017.59","article-title":"PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: Inter-pathologist variability is higher than assay variability","volume":"30","author":"Brunnstrom","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/j.jtho.2017.07.031","article-title":"Multicenter Comparison of 22C3 PharmDx (Agilent) and SP263 (Ventana) Assays to Test PD-L1 Expression for NSCLC Patients to Be Treated with Immune Checkpoint Inhibitors","volume":"12","author":"Marchetti","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3585","DOI":"10.1158\/1078-0432.CCR-16-2375","article-title":"Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non-Small Cell Lung Cancer","volume":"23","author":"Ratcliffe","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/modpathol.2015.65","article-title":"BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations","volume":"28","author":"Cigognetti","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1097\/PAS.0000000000000616","article-title":"BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas","volume":"40","author":"Hwang","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.anndiagpath.2016.10.010","article-title":"Usefulness of p16\/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma","volume":"26","author":"Wu","year":"2017","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1309\/AJCPT94JVWIHBKRD","article-title":"Diagnostic usefulness of p16\/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis","volume":"139","author":"Wu","year":"2013","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5858\/arpa.2017-0124-RA","article-title":"Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group","volume":"142","author":"Husain","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1097\/PAS.0000000000000852","article-title":"Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma","volume":"41","author":"Kuraoka","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/modpathol.2016.181","article-title":"MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma","volume":"30","author":"Amatya","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1097\/JTO.0000000000000545","article-title":"Primary Pulmonary NUT Midline Carcinoma: Clinical, Radiographic, and Pathologic Characterizations","volume":"10","author":"Sholl","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1158\/1078-0432.CCR-12-1153","article-title":"Clinicopathologic features and long-term outcomes of NUT midline carcinoma","volume":"18","author":"Bauer","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1200\/JCO.2004.02.107","article-title":"Midline carcinoma of children and young adults with NUT rearrangement","volume":"22","author":"French","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_97","first-page":"304","article-title":"BRD4-NUT fusion oncogene: A novel mechanism in aggressive carcinoma","volume":"63","author":"French","year":"2003","journal-title":"Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1038\/sj.onc.1210852","article-title":"BRD-NUT oncoproteins: A family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells","volume":"27","author":"French","year":"2008","journal-title":"Oncogene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1158\/2159-8290.CD-14-0014","article-title":"NSD3-NUT fusion oncoprotein in NUT midline carcinoma: Implications for a novel oncogenic mechanism","volume":"4","author":"French","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev-pathol-011811-132438","article-title":"Pathogenesis of NUT midline carcinoma","volume":"7","author":"French","year":"2012","journal-title":"Annu. Rev. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12105-013-0428-1","article-title":"The importance of diagnosing NUT midline carcinoma","volume":"7","author":"French","year":"2013","journal-title":"Head Neck Pathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1158\/2159-8290.CD-15-1335","article-title":"Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015\/MK-8628","volume":"6","author":"Stathis","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1158\/2159-8290.CD-17-0605","article-title":"BET Proteins as Targets for Anticancer Treatment","volume":"8","author":"Stathis","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1097\/PAS.0b013e318198d666","article-title":"Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody","volume":"33","author":"Haack","year":"2009","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.1365-2303.2010.00838.x","article-title":"NUT midline carcinoma: A neoplasm with diagnostic challenges in cytology","volume":"22","author":"Zhu","year":"2011","journal-title":"Cytopathology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1097\/PAS.0b013e318258f03b","article-title":"Pathologic characteristics of NUT midline carcinoma arising in the mediastinum","volume":"36","author":"Evans","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"411","DOI":"10.4132\/jptm.2016.08.08","article-title":"Immunohistochemistry for Pathologists: Protocols, Pitfalls, and Tips","volume":"50","author":"Kim","year":"2016","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.5858\/arpa.2013-0691-RA","article-title":"A review of preanalytical factors affecting molecular, protein, and morphological analysis of formalin-fixed, paraffin-embedded (FFPE) tissue: How well do you know your FFPE specimen?","volume":"138","author":"Bass","year":"2014","journal-title":"Arch. Pathol. Lab. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/3\/72\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:04Z","timestamp":1760194624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/3\/72"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,14]]},"references-count":108,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["cancers10030072"],"URL":"https:\/\/doi.org\/10.3390\/cancers10030072","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,14]]}}}