{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T07:20:46Z","timestamp":1776928846847,"version":"3.51.2"},"reference-count":43,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"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>Background\/Objectives: MOC31 immunostain identifies carcinoma cells and is often used in effusion fluid cytology. This systematic review and meta-analysis aim to detail the diagnostic performance of MOC31 with subgroup analysis for different types of carcinomas. Methods: A literature search from five databases was performed. Relevant studies were reviewed for the calculation of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve of hierarchical summary receiver operating characteristics (AUC-HSROC). Risk of bias, heterogeneity, and publication bias were assessed by the QUADAS-2, I2 index, and Deeks\u2019 funnel plot. Results: In total, 25 studies (10 retrospective cohorts, 10 case\u2013control studies, and 5 case series) were included. The pooled sensitivity, specificity, NLR, PLR, and DOR were 0.926 (0.827\u20130.971), 0.932 (0.883\u20130.961), 0.079 (0.005\u20130.152), 13.610 (5.327\u201321.892), and 172.475 (83.150\u2013428.100), respectively. The AUC-HSROC was 0.975, indicating excellent performance. Further analysis for adenocarcinomas, mesotheliomas, and benign\/reactive mesothelial cells showed sensitivity for adenocarcinomas at 0.962 (0.948\u20130.975) and specificity for mesotheliomas and mesothelial cells at 0.934 (0.900\u20130.967) and 0.997 (0.994\u20131.000). Sensitivity in all four primary site subgroups (female genital, gastrointestinal\/hepatobiliary, lung and breast) of adenocarcinoma were high (&gt;0.910). Heterogeneity was observed, and meta-regression identified a trend for the year of publication. No evidence of publication bias was observed. Conclusions: Evidence shows that MOC31 could be a robust immunocytochemical marker for identifying and excluding metastatic carcinoma, with excellent diagnostic performance across types of adenocarcinomas. However, evidence is mainly from retrospective studies, highlighting the need for high-quality evidence to further establish MOC31diagnostic utility.<\/jats:p>","DOI":"10.3390\/diagnostics15212675","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:47:36Z","timestamp":1761266856000},"page":"2675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MOC31 for the Diagnosis of Metastatic Carcinoma and Mesothelial Lesions in Effusion Fluid\u2014A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Alex H.","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna K. M.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahar J.","family":"Farahani","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renald","family":"Me\u00e7ani","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetology, Medical University of Graz, 8010 Graz, Austria"},{"name":"Epistudia, 3008 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Nano","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, TUM School of Medicine and Health, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua J. X.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2574-3241","authenticated-orcid":false,"given":"Philippe","family":"Vielh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medipath and American Hospital of Paris, 92200 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3235-3073","authenticated-orcid":false,"given":"Taulant","family":"Muka","sequence":"additional","affiliation":[{"name":"Epistudia, 3008 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s002620050348","article-title":"A novel immunotoxin recognising the epithelial glycoprotein-2 has potent antitumoural activity on chemotherapy-resistant lung cancer","volume":"44","author":"Zimmermann","year":"1997","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/imj.15725","article-title":"Evaluation of pleural fluid cytology for the diagnosis of malignant pleural effusion: A retrospective cohort study","volume":"52","author":"Pairman","year":"2022","journal-title":"Intern. Med. J."},{"key":"ref_3","first-page":"PA4308","article-title":"Pleural fluid \u2018cell block\u2019 analysis in malignant pleural effusion: Sensitive, superior over fluid cytology and suitable for immunohistochemistry analysis (IHC), will decrease need for thoracoscopy guided procedures","volume":"50","author":"Shital","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1002\/cam4.5038","article-title":"A comparative study of diagnostic accuracy in 3026 pleural biopsies and matched pleural effusion cytology with clinical correlation","volume":"12","author":"Poon","year":"2023","journal-title":"Cancer Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/dc.25393","article-title":"Comparison of Claudin-4, BerEP4, Carcinoembryonic Antigen and MOC31 in Serous Fluids Metastases Demonstrate High Sensitivity of Claudin-4 at Low Cellularity","volume":"52","author":"Li","year":"2024","journal-title":"Diagn. Cytopathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e22910","DOI":"10.1002\/cncy.22910","article-title":"Single-cell multiplex immunocytochemistry in cell block preparations of metastatic breast cancer confirms sensitivity of GATA-binding protein 3 over gross cystic disease fluid protein 15 and mammaglobin","volume":"133","author":"Li","year":"2025","journal-title":"Cancer Cytopathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/cyt.13493","article-title":"Performance of the Monoclonal Antibody B72.3 in Diagnosis of Malignant Carcinomatous Serous Effusions-A Systematic Review and Meta-Analysis of Diagnostic Performance","volume":"36","author":"Lin","year":"2025","journal-title":"Cytopathology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1001\/jama.2017.19163","article-title":"Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement","volume":"319","author":"McInnes","year":"2018","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"529","DOI":"10.7326\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2: A revised tool for the quality assessment of diagnostic accuracy studies","volume":"155","author":"Whiting","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000527789","article-title":"Diagnosis of Metastatic Carcinoma Using Body Cavity Fluid Specimens: A Comparison of Diagnostic Panels","volume":"67","author":"Sridakhun","year":"2023","journal-title":"Acta Cytol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/cncy.22672","article-title":"The utility of claudin-4 versus MOC-31 and Ber-EP4 in the diagnosis of metastatic carcinoma in cytology specimens","volume":"131","author":"Najjar","year":"2023","journal-title":"Cancer Cytopathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1159\/000515173","article-title":"MOC31 Immunostaining in the Diagnosis of Metastatic Adenocarcinoma in Serous Fluid: Special Emphasis on Atypical Cytological Cases","volume":"65","author":"Sahu","year":"2021","journal-title":"Acta Cytol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/JOC.JOC_13_18","article-title":"Use of Panel of Markers in Serous Effusion to Distinguish Reactive Mesothelial Cells from Adenocarcinoma","volume":"36","author":"Subbarayan","year":"2019","journal-title":"J. Cytol."},{"key":"ref_15","first-page":"2019","article-title":"Anti-EpCAM antibodies for detection of metastatic carcinoma in effusions and peritoneal wash","volume":"18","author":"Carneiro","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/dc.23653","article-title":"The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions","volume":"45","author":"Sadullahoglu","year":"2017","journal-title":"Diagn. Cytopathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/dc.23476","article-title":"Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology","volume":"44","author":"Oda","year":"2016","journal-title":"Diagn. Cytopathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/dc.23218","article-title":"Expression and significance of MOC-31 and calretinin in pleural fluid of patients with lung cancer","volume":"43","author":"Lv","year":"2015","journal-title":"Diagn. Cytopathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/dc.22852","article-title":"The application of immunocytochemistry to direct smears in the diagnosis of effusions","volume":"41","author":"Knoepp","year":"2013","journal-title":"Diagn. Cytopathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1159\/000339586","article-title":"The diagnostic utility of D2-40, calretinin, CK5\/6, desmin and MOC-31 in the differentiation of mesothelioma from adenocarcinoma in pleural effusion cytology","volume":"56","author":"Hyun","year":"2012","journal-title":"Acta Cytol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/dc.21489","article-title":"Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry","volume":"39","author":"Su","year":"2011","journal-title":"Diagn. Cytopathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/cncy.20164","article-title":"Use of the monoclonal antibody MOC-31 as an immunomarker for detecting metastatic adenocarcinoma in effusion cytology","volume":"119","author":"Kundu","year":"2011","journal-title":"Cancer Cytopathol."},{"key":"ref_23","first-page":"95","article-title":"Accuracy of immunohistochemistry in evaluation of malignant pleural and peritoneal effusions","volume":"62","author":"Ensani","year":"2011","journal-title":"Pol. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/dc.21006","article-title":"Differentiating reactive mesothelial cells from metastatic adenocarcinoma in serous effusions: The utility of immunocytochemical panel in the differential diagnosis","volume":"37","author":"Saleh","year":"2009","journal-title":"Diagn. Cytopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1159\/000325401","article-title":"Diagnostic utility of MOC-31, HBME-1 and MOC-31 mRNA in distinguishing between carcinoma cells and reactive mesothelial cells in pleural effusions","volume":"53","author":"Sun","year":"2009","journal-title":"Acta Cytol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/dc.20986","article-title":"Immunocytochemical panel for distinguishing between adenocarcinomas and reactive mesothelial cells in effusion cell blocks","volume":"37","author":"Kim","year":"2009","journal-title":"Diagn. Cytopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/dc.20747","article-title":"Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5\/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions","volume":"36","author":"Pu","year":"2008","journal-title":"Diagn. Cytopathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.5858\/2008-132-23-CMVBHU","article-title":"Cytologic malignancy versus benignancy: How useful are the \u201cnewer\u201d markers in body fluid cytology?","volume":"132","author":"Mody","year":"2008","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/cncr.21426","article-title":"Monoclonal antibody MOC-31 reactivity as a marker for adenocarcinoma in cytologic preparations","volume":"108","author":"Hecht","year":"2006","journal-title":"Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/dc.20203","article-title":"Immunocytochemical panel for distinguishing between carcinoma and reactive mesothelial cells in body cavity fluids","volume":"32","author":"Politi","year":"2005","journal-title":"Diagn. Cytopathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/1097-0142(20010225)93:1<68::AID-CNCR9009>3.0.CO;2-F","article-title":"Immunocytochemistry in the differential diagnosis of serous effusions: A comparative evaluation of eight monoclonal antibodies in Papanicolaou stained smears","volume":"93","author":"Lozano","year":"2001","journal-title":"Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/BF03032357","article-title":"Moc-31, fibronectin and CEA in the differential diagnosis of malignant effusions: An immunocytochemical study","volume":"6","author":"Athanassiadou","year":"2000","journal-title":"Pathol. Oncol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/(SICI)1097-0339(199708)17:2<115::AID-DC6>3.0.CO;2-F","article-title":"Complementary value of five carcinoma markers for the diagnosis of malignant mesothelioma, adenocarcinoma metastasis, and reactive mesothelium in serous effusions","volume":"17","author":"Delahaye","year":"1997","journal-title":"Diagn. Cytopathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1159\/000333902","article-title":"Quality control of immunocytochemical staining of effusions using a standardized method of cell processing","volume":"40","year":"1996","journal-title":"Acta Cytol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/path.1711650209","article-title":"Immunocytochemistry of malignant mesothelioma: OV632 as a marker of malignant mesothelioma","volume":"165","author":"Delahaye","year":"1991","journal-title":"J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.21037\/amj-2019-mpe-05","article-title":"Etiopathogenesis of malignant pleural effusion","volume":"6","author":"Jovanovic","year":"2020","journal-title":"AME Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/dc.24151","article-title":"Cytologic diagnosis of metastatic malignant phyllodes tumor of the breast in pleural effusion","volume":"47","author":"Li","year":"2019","journal-title":"Diagn. Cytopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.lungcan.2022.10.013","article-title":"EGFR testing in paraffin-embedded cell block cytology material is reliable with increased detection for effusion fluid","volume":"174","author":"Ng","year":"2022","journal-title":"Lung Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/cyt.13175","article-title":"Cell block-based RNA next generation sequencing for detection of gene fusions in lung adenocarcinoma: An institutional experience","volume":"34","author":"Wei","year":"2023","journal-title":"Cytopathology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"975","DOI":"10.21037\/tlcr-24-979","article-title":"Recent advancements in lung cancer research: A narrative review","volume":"14","author":"Tang","year":"2025","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13048-025-01657-8","article-title":"Malignant ascites in ovarian cancer is compatible with long-term (10 year) survival with associations to clinicopathological features","volume":"18","author":"Chow","year":"2025","journal-title":"J. Ovarian Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"381","DOI":"10.5858\/arpa.2023-0560-RA","article-title":"The Diagnostic Accuracy of Claudin-4 Immunochemistry in Differentiating Metastatic Carcinomas From Mesothelial Processes in Serous Effusion Cytology: A Systematic Review and Meta-analysis","volume":"149","author":"Kleinaki","year":"2025","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1177\/10668969241261552","article-title":"Neuroendocrine Lesions Arising From Mediastinal Teratoma\u2014A Case Report and Literature Review","volume":"33","author":"Lam","year":"2025","journal-title":"Int. J. Surg. Pathol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2675\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T01:04:38Z","timestamp":1761267878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":43,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["diagnostics15212675"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15212675","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}