Background: Claudin-4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin-4 versus MOC-31 and Ber-EP4 by comparing their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens.
Methods: This retrospective study comprised a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine-needle aspiration specimens. Cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign. Cell block sections were stained for claudin-4 and compared with those previously stained for MOC-31 and Ber-EP4. Indefinite cases were further reclassified based on clinical and pathologic findings into benign (26 cases), mesothelioma (11 cases), and carcinoma (nine cases).
Results: None of the mesotheliomas (0/39) or benign effusions (0/47) were positive for claudin-4, whereas 134 of the 143 carcinoma specimens were positive. Compared to MOC-31 and Ber-EP4, claudin-4 had the highest specificity and PPV (100% for each), followed by Ber-EP4. Claudin-4 showed high sensitivity (93.7%), albeit lower than MOC-31. MOC-31 had the lowest specificity and PPV but the highest sensitivity and NPV. Ber-EP4 had the lowest sensitivity (91.6%).
Conclusions: Claudin-4 can be used as a single marker for carcinoma with high sensitivity and superior specificity compared with MOC-31 and Ber-EP4. Mesothelial lineage can be ruled out when claudin-4 is positive. In equivocal cytology samples with few scattered cells of interest, a panel of claudin-4 and Ber-EP4 results in the highest combined sensitivity and specificity.
Keywords: Ber-EP4; MOC-31; claudin-4; effusion cytopathology; mesothelioma; mesothelioma versus metastatic carcinoma; metastatic carcinoma.
© 2022 American Cancer Society.