Diagnostic value of claudin-4 marker in pleural and peritoneal effusion cytology: Does it differentiate between metastatic adenocarcinoma and reactive mesothelial cells?

Abstract

Background: Several markers have been used to make a distinction between metastatic adenocarcinoma and reactive mesothelial cells in the body cavity effusions. This study aimed to evaluate the diagnostic value of claudin-4 marker in making such a distinction. Materials and Methods: In this cross-sectional study, a total of 92 pleural/peritoneol effusions have been studied, including 47 cases of definite metastatic carcinoma and 45 cases of reactive mesothelium, and definitely negative for malignancy. Specimens were collected from patients; cell block samples were derived and used for immunohistochemical staining. The antibody used for immunohistochemical labeling was monoclonal anti-claudin-4. In the evaluation, membrane-bound reactivity was considered as significant and positive cases were defined when at least more than 10% of tumor cells were distinctly labeled. Results: Claudin-4 protein was positive in 40 specimens of metastatic carcinoma, while none of the cases of reactive mesothelium stained with the marker. This was not detected in the mesothelial cells, though. Positive staining for claudin-4 was significantly more frequent in metastatic carcinoma than in the reactive mesothelium (P > 0.0001). The sensitivity and specificity of claudin-4 to distinguish reactive mesothelium from metastatic carcinoma were 85% (95% confidence interval [CI], 71.1-93.8%) and 100% (95% CI, 91.1-100%), respectively. Furthermore, negative likelihood ratio was 0.15 (95% CI, 0.08-0.29). Conclusion: The results of this study demonstrated that claudin-4 is less frequently expressed in reactive mesothelium. Thus, this claudin may be helpful in differentiating metastatic carcinoma from reactive mesothelial cells in pleural and peritoneal fluid cytology specimen.