Claudin-4

Claudin-4 is a protein found in the tight junctions between cells that line body cavities and organs (epithelial cells). Pathologists use antibodies against claudin-4 as a stain in tissue samples to help tell carcinomas (cancers of epithelial origin) apart from mesothelioma, because carcinomas usually stain strongly positive while mesotheliomas are almost always negative.

Origin

The claudin family of tight-junction proteins was first described in 1998 by Japanese researchers Mikio Furuse and Shoichiro Tsukita, who named them from the Latin claudere, meaning "to close," reflecting their role in sealing the space between cells. Claudin-4 was identified as a useful diagnostic marker for distinguishing carcinoma from mesothelioma in pathology studies during the late 2000s.

Significance in Asbestos Context

For a patient being worked up for possible mesothelioma, claudin-4 is one of the immunohistochemical (IHC) stains a pathologist may run on a biopsy to confirm the diagnosis. Mesothelioma can look very similar under the microscope to adenocarcinoma that has spread to the pleura or peritoneum from the lung, breast, ovary, or other organ, and the treatment and legal implications differ greatly between the two. A negative claudin-4 result supports a diagnosis of mesothelioma, while a strongly positive result points toward metastatic carcinoma instead. Because an accurate mesothelioma diagnosis is the foundation of both treatment planning and any asbestos claim, patients should make sure their pathology report lists the specific IHC markers used, including claudin-4 when applicable.

Example Sentence

The pathologist reported that the pleural biopsy was negative for claudin-4 and positive for calretinin and WT-1, supporting a diagnosis of epithelioid mesothelioma rather than metastatic lung adenocarcinoma.

Related Terms

Immunohistochemistry, Calretinin, WT-1, BAP1, Mesothelioma, Epithelioid Mesothelioma

Notes

• Ask your oncologist or pathologist for a copy of your full pathology report, including the list of IHC stains performed and their results. Claudin-4, calretinin, WT-1, BAP1, and others are typically listed.
• If your diagnosis is uncertain or based on a limited panel, request a second opinion from a mesothelioma specialty center (such as a National Cancer Institute–designated cancer center), which may run additional or repeat stains on the same tissue block.
• Preserve the original biopsy tissue blocks and slides; these may be needed for further testing, treatment decisions, or expert review in connection with a legal claim.
• Claudin-4 is most useful in epithelioid tumors; sarcomatoid mesotheliomas have a different staining profile, so the panel used should match the suspected subtype.