{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T13:35:56Z","timestamp":1785677756667,"version":"3.56.0"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal\/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41\/41 SMs, while it was positive in 18\/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23\/41 SMs, while it was regularly expressed in 46\/46 SCs. All the cases of the normal\/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low\/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM.<\/jats:p>","DOI":"10.3390\/diagnostics13020249","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T01:30:47Z","timestamp":1673314247000},"page":"249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immunohistochemistry for Claudin-4 and BAP1 in the Differential Diagnosis between Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma"],"prefix":"10.3390","volume":"13","author":[{"given":"Lina","family":"Zuccatosta","sequence":"first","affiliation":[{"name":"Pulmonary Diseases Unit, Azienda \u201cOspedali Riuniti\u201d, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Bizzarro","sequence":"additional","affiliation":[{"name":"Operative Unit of Pathologic Anatomy, Azienda USL Della Romagna, Infermi Hospital, 47900 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-1218","authenticated-orcid":false,"given":"Giulio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Pathologic Anatomy Unit, Fondazione Poliambulanza, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Gallo","sequence":"additional","affiliation":[{"name":"Operative Unit of Pathologic Anatomy, Azienda USL della Romagna, \u201cBufalini\u201d Hospital, 47521 Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Pulmonary Diseases Unit, Azienda \u201cOspedali Riuniti\u201d, 60126 Ancona, Italy"},{"name":"Department of Biomedical Sciences and Public Health, Polytechnic University of Marche Region, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7800-4229","authenticated-orcid":false,"given":"Andrea","family":"Ambrosini-Spaltro","sequence":"additional","affiliation":[{"name":"Pathology Unit, Azienda USL della Romagna, Morgagni-Pierantoni Hospital, 47100 Forl\u00ec, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5146\/tjpath.2013.01210","article-title":"The Diagnosis of Thoracic Malignant Mesothelioma: Practical Considerations and Recent Developments","volume":"30","author":"Smith","year":"2014","journal-title":"Turk. J. Pathol."},{"key":"ref_2","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":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/cncy.22368","article-title":"The \u201cBrescia Panel\u201d (Claudin-4 and BRCA-associated Protein 1) in the Differential Diagnosis of Mesotheliomas with Epithelioid Features versus Metastatic Carcinomas","volume":"129","author":"Bernardi","year":"2021","journal-title":"Cancer Cytopathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/PAP.0000000000000180","article-title":"Recent Advances in the Diagnosis of Malignant Mesothelioma: Focus on Approach in Challenging Cases and in Limited Tissue and Cytologic Samples","volume":"25","author":"Monaco","year":"2018","journal-title":"Adv. Anat. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1177\/10668969211014256","article-title":"Sarcomatoid Mesothelioma: A Clinicopathological and Immunohistochemical Study of 64 Cases","volume":"29","author":"Oramas","year":"2021","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.humpath.2017.07.015","article-title":"The Differential Diagnosis between Pleural Sarcomatoid Mesothelioma and Spindle Cell\/Pleomorphic (Sarcomatoid) Carcinomas of the Lung: Evidence-Based Guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center","volume":"67","author":"Marchevsky","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rossi, G., Davoli, F., Poletti, V., Cavazza, A., and Lococo, F. (2021). When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines. J. Clin. Med., 10.","DOI":"10.3390\/jcm10112434"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.21037\/tlcr.2019.11.29","article-title":"Application of Immunohistochemistry in Diagnosis and Management of Malignant Mesothelioma","volume":"9","author":"Chapel","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1097\/PAS.0000000000000825","article-title":"GATA3 Immunohistochemistry for Distinguishing Sarcomatoid and Desmoplastic Mesothelioma from Sarcomatoid Carcinoma of the Lung","volume":"41","author":"Berg","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00428-021-03048-y","article-title":"GATA3 Is a Useful Immunohistochemical Marker for Distinguishing Sarcomatoid Malignant Mesothelioma from Lung Sarcomatoid Carcinoma and Organizing Pleuritis","volume":"479","author":"Piao","year":"2021","journal-title":"Virchows Arch."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humpath.2020.08.005","article-title":"The Potential Utility of GATA Binding Protein 3 for Diagnosis of Malignant Pleural Mesotheliomas","volume":"105","author":"Prabhakaran","year":"2020","journal-title":"Hum. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"208","DOI":"10.5858\/arpa.2019-0647-OA","article-title":"Utility of Immunohistochemistry for MUC4 and GATA3 to Aid in the Distinction of Pleural Sarcomatoid Mesothelioma From Pulmonary Sarcomatoid Carcinoma","volume":"145","author":"Terra","year":"2021","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_13","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_14","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_15","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/path.5551","article-title":"Large-scale Analysis of BAP1 Expression Reveals Novel Associations with Clinical and Molecular Features of Malignant Pleural Mesothelioma","volume":"253","author":"Chirieac","year":"2021","journal-title":"J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"153267","DOI":"10.1016\/j.prp.2020.153267","article-title":"Sarcomatoid Mesothelioma: A CDKN2A Molecular Analysis of 53 Cases with Immunohistochemical Correlation with BAP1","volume":"216","author":"Zaleski","year":"2020","journal-title":"Pathol.-Res. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.lungcan.2016.12.017","article-title":"Immunohistochemical Detection of MTAP and BAP1 Protein Loss for Mesothelioma Diagnosis: Comparison with 9p21 FISH and BAP1 Immunohistochemistry","volume":"104","author":"Hida","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.lungcan.2018.09.019","article-title":"A Combination of MTAP and BAP1 Immunohistochemistry Is Effective for Distinguishing Sarcomatoid Mesothelioma from Fibrous Pleuritis","volume":"125","author":"Kinoshita","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/ajcp\/aqab091","article-title":"Loss of Methylthioadenosine Phosphorylase by Immunohistochemistry Is Common in Pulmonary Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma","volume":"157","author":"Terra","year":"2022","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_20","unstructured":"WHO Classification of Tumours Editorial Board (2021). Thoracic Tumours. WHO Classification of Tumours Series, IARC Press. [5th ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1136\/jcp.2005.028589","article-title":"Claudins in Differential Diagnosis between Mesothelioma and Metastatic Adenocarcinoma of the Pleura","volume":"59","author":"Soini","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"ref_22","first-page":"47","article-title":"Claudins: Gatekeepers of Lung Epithelial Function","volume":"42","author":"Schlingmann","year":"2015","journal-title":"Claudins"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s00428-007-0448-x","article-title":"Claudin 4 Identifies a Wide Spectrum of Epithelial Neoplasms and Represents a Very Useful Marker for Carcinoma versus Mesothelioma Diagnosis in Pleural and Peritoneal Biopsies and Effusions","volume":"451","author":"Facchetti","year":"2007","journal-title":"Virchows Arch."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jasc.2019.12.003","article-title":"Utility of Claudin-4 versus BerEP4 and B72.3 in Pleural Fluids with Metastatic Lung Adenocarcinoma","volume":"9","author":"Patel","year":"2020","journal-title":"J. Am. Soc. Cytopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/cyt.12765","article-title":"Claudin-4 Immunohistochemistry Is a Useful Pan-Carcinoma Marker for Serous Effusion Specimens","volume":"30","author":"Vojtek","year":"2019","journal-title":"Cytopathology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.humpath.2020.04.005","article-title":"Claudin-4 Shows Superior Specificity for Mesothelioma vs Non\u2013Small-Cell Lung Carcinoma Compared with MOC-31 and Ber-EP4","volume":"100","author":"Naso","year":"2020","journal-title":"Hum. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1309\/AJCP0B3YJBXWXJII","article-title":"Value of Claudin-4 Immunostaining in the Diagnosis of Mesothelioma","volume":"139","year":"2013","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/his.14110","article-title":"SWI\/SNF Protein and Claudin-4 Expression in Anaplastic Carcinomas Arising in Mucinous Tumours of the Ovary and Retroperitoneum","volume":"77","author":"Chaudet","year":"2020","journal-title":"Histopathology"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/2\/249\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:04:53Z","timestamp":1760119493000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/2\/249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,9]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["diagnostics13020249"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13020249","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,9]]}}}