Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens

To evaluate the utility of claudin-4 as a pan-carcinoma marker in cell-blocks of effusion specimens and compare results with Ber-Ep4 staining.

Effusion cell-blocks (n = 284) were stained for claudin-4 and results compared with Ber-Ep4. Cases included 172 metastatic malignancies (137 adenocarcinomas, 20 small cell lung tumours, eight metastatic melanoma, four squamous cell carcinoma, three urothelial cell carcinoma), 49 benign reactive cases and 63 mesotheliomas.

All 49 benign effusions were negative. Only 1/63 (1.6%) mesotheliomas was positive for claudin-4. Claudin-4 staining was positive in 131/137 (95.6%) adenocarcinoma cases. Cases negative for claudin-4 included single cases of metastases from breast, colon, stomach, prostate, kidney and ovary. Claudin-4 outperformed Ber-Ep4. Sensitivity (95.6% vs 85.4%), specificity (99.1% vs 86.6%), negative predictive value (94.9% vs 82.9%) and positive predictive value (99.2% vs 88.6%) were all higher for claudin-4 compared with Ber-Ep4, respectively. Only two cases were claudin-4-/Ber-Ep4+. Significantly (P < .0064) more cases of metastatic adenocarcinoma stained positive for claudin-4 (131/137; 95.6%) than Ber-Ep4 (117/137; 86.2%). Claudin-4 staining was present in 15/20 (75%) of neuroendocrine carcinomas, 3/4 (75%) squamous cell carcinoma and 3/3 (100%) urothelial cell carcinoma. All eight cases of melanoma were negative for both claudin-4 and Ber-Ep4.

Claudin-4 staining is a useful addition to IHC panels for effusions specimens with superior performance to Ber-Ep4.