Correlation patterns of CEA, CA19-9, CA72-4, CA125, CA15-3, and PIVKA-II in malignant pleural effusions: overlap and distinction across tumor biology

Introduction : Malignant pleural effusions (MPEs) are a frequent complication of cancer, causing significant morbidity and representing a major diagnostic challenge. Tumor markers in pleural fluid have been studied, but their interrelationships remain poorly understood. Aim : To investigate the correlations among commonly used tumor markers in pleural effusions and to assess their potential role in differentiating malignant from benign cases. Materials and methods : A cross-sectional case-control study was conducted on 151 Bulgarian patients with hydrothorax. The control group consisted of 72 patients with benign pleural effusions (38 inflammatory, 34 non-inflammatory), while 79 patients had malignant pleural involvement. Correlation analysis was applied to evaluate the relationships between carcinoembryonic antigen (CEA), CA19-9, CA72-4, CA125, CA15-3, and PIVKA-II. Results : Significant moderate positive correlations were found between CEA, CA19-9, CA72-4, and CA125, indicating overlapping tumor biology. CA125 also correlated with CA15-3, consistent with their role in epithelial malignancies. In contrast, PIVKA-II showed no significant correlation with other markers, suggesting limited utility in pleural malignancy diagnosis. These findings point to both redundancy and complementarity among tumor markers. Conclusions : Tumor markers in pleural fluid, particularly CEA, CA125, CA19-9, and CA72-4, may provide valuable diagnostic information when assessed together. Their interrelationships support the rational selection of marker panels to improve diagnostic accuracy for MPEs. PIVKA-II appears less informative in this setting. Understanding these correlations may enhance minimally invasive diagnostic strategies and contribute to more personalized management of pleural malignancy.