MD Doctor of Medicine

Introduction: The distinction between mesotheliomas and metastatic carcinomas in serous cavities is still a perplexing topic. The present biomarkers of the immunohistochemical panel do not provide solution to this obstacle, since no current biomarker has the adequate specificity and sensitivity to effectively diagnose metastasis in either peritoneal, pericardial, or pleural cavities. Claudin-4, a tight junction transmembrane protein, is a promising biomarker to fill this diagnostic gap due to its selective presence in epithelial and absence in mesothelial cells. Purpose: The purpose of this meta-analysis was to gather all the available data from the present literature and present an overall result for the diagnostic accuracy of claudin-4, as a biomarker of metastasis in serous cavities. Methodology: The meta-analysis was performed based on the PRISMA 2020 statement. The keywords claudin-4, immunohistochemistry, pleural effusion, peritoneal effusion, ascitic effusion, pericardial effusion, and mesothelioma were used to search for relevant articles in PubMed and Scopus. The pre-specified inclusion criteria included original studies reporting Claudin-4 immunohistochemistry or immunocytochemistry in body cavities (pleural, peritoneal, pericardial). A meta-analysis was conducted to estimate the sensitivity, specificity, and diagnostic odds ratio of claudin-4 in pleural, peritoneal, ascitic, and pericardial effusions. Results: Claudin 4 demonstrated high numbers of sensitivity (98.42%) and specificity (99.58%) in diagnosing metastatic carcinomas and differentiating them from malignant mesotheliomas and reactive mesothelial cells. The Diagnostic Odd Ratio (DOR) of this transmembrane biomarker was 1779.9, and the high diagnostic accuracy of claudin 4 as a metastasis detector was further highlighted. No heterogeneity or publication bias of the included studies were observed in this meta-analysis. Conclusion: This was the first systematic presentation of claudin 4 as a biomarker of cytopathological diagnosis. Its diagnostic accuracy in detecting metastasis in serous cavities was clearly depicted. The high numbers of sensitivity and specificity proved the initial research hypothesis and the aim of this metanalysis was achieved.