CLDN4

Claudin-4, encoded by the CLDN4 gene on chromosome 7q11.23, is a tight junction protein critical for epithelial barrier function. The immunohistochemical expression pattern is membraneous.

Claudin-4 is a membrane-bound protein present in most epithelial cells but absent in mesothelial cells, making it a highly specific marker for distinguishing lung adenocarcinomas (positive for claudin-4) from mesotheliomas (negative for claudin-4).
Claudin-4 has in publications demonstrated exceptional diagnostic specificity in the differential diagnosis of mesothelioma versus lung adenocarcinoma . Only 0.1% of mesotheliomas express claudin-4, compared to 93% of non-small-cell lung carcinomas and 92% of other carcinomas.
Adding HEG1 to claudin-4 staining can further increase diagnostic specificity. A HEG1-positive/Claudin-4-negative result supports a mesothelioma diagnosis, while a Claudin-4-positive/HEG1-negative result indicates carcinoma. Claudin-4 has comparable diagnostic sensitivity to MOC31 and EP4 for carcinomas but a significantly superior diagnostic specificity for carcinoma versus mesotheliomas.

• Distinguishing mesotheliomas from other epithelial neoplasms.
• Identification of epithelial cells.

Placenta and colon/appendix tissues are recommended as positive and negative tissue controls for claudin-4. In placenta, most cytotrophoblasts should exhibit at least a weak membranous staining reaction to evaluate the limit of detection and analytical sensitivity. In colon/appendix, virtually all epithelial cells should display a moderate to strong membranous staining reaction. No staining should be observed in lymphocytes or muscle cells in these tissues ensuring analytical specificity.