Diagnostic Cytopathology 2023 October 13 [Link]
Vanlal Hruaii, Balamurugan Thirunavukkarasu, Vindhya Prabha, Sandeep Mathur, Venkateswaran K Iyer, Aruna Nambirajan, Deepali Jain
Background: Claudin-4, a tight junction associated protein expressed in epithelial cells, is purported as a highly specific and sensitive marker for epithelial malignancies. Our aim was to assess the sensitivity, specificity and real-time utility of claudin-4 immunocytochemistry (ICC) in the diagnostic work-up of suspected malignant effusions.
Methods: Claudin-4 (3E2C1 clone) ICC was performed prospectively in effusion cell blocks where other ICC markers were being performed as part of reporting over 3 months. Based on claudin-4 staining in unequivocal malignant and reactive effusions, the sensitivity and specificity was calculated. In cases signed out as inconclusive encompassing atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) and negative for malignancy, change in diagnostic category based on addition of claudin-4 ICC was assessed.
Results: Study included 107 effusions. Claudin-4 stained 100% of metastatic adenocarcinomas including those with primaries in lung, breast, ovary, female genital tract, gastrointestinal tract and pancreatic-biliary tract, and was negative in all reactive mesothelial and mesothelioma effusions with sensitivity of 100% (48/48) and specificity of 95% (20/21) for adenocarcinoma. Claudin-4 upgraded the diagnostic category to positive in 70% (16/23) of SFM, 20% (1/5) of AUS, and in 50% (5/10) of negative effusions. Among cases with confirmed serosal involvement status on follow-up, claudin-4 showed sensitivity, specificity, positive predictive value and negative predictive values of 85% (11/13), 100% (3/3), 100% (10/10) and 75% (3/4), respectively, for metastatic adenocarcinoma.
Conclusion: Claudin-4 as a single marker is sensitive and specific for adenocarcinoma and is a valuable addition to the ICC armamentarium.