All IHC stains will include a positive control tissue

Claudin-4 should be used as part of a panel of immunohistochemical stains to evaluate neoplasms of epithelial differentiation from benign mesothelial cells and mesothelial neoplasms. Claudin-4 has a reported sensitivity ranging from 91-100% and a specificity of 94-100% for epithelial neoplasms. Rare mesothelial lesions and benign mesothelial cells have been reported to show focal granular cytoplasmic (not membranous) positivity. ^1-3 See tables 1 and 2 below from the Facchetti et al article which outlines Claudin-4 reactivity in normal tissue and various neoplasms.²

In cytology specimens, Claudin-4 has been shown to have higher sensitivity and specificity than BerEP4 and MOC31.^4-6

Table 1: Claudin-4 expression in normal tissues²

Table 2: Claudin-4 expression in various tumors²

Submit a formalin-fixed, paraffin-embedded tissue

Formalin-fixed, paraffin-embedded (FFPE) tissue block

FFPE tissue section mounted on a charged, unstained slide

Ambient (preferred)

• Unlabeled/mislabeled block
• Insufficient tissue
• Slides broken beyond repair

Immunohistochemical staining and microscopic examination

If requested, and interpretive report will be provided

Specifications

Claudin-4 is one of 27 proteins that comprise functional constituents of epithelial tight junctions, which are expressed in the majority of epithelial cells. These proteins are present at epithelial and endothelial cell interfaces are responsible for ion flux, recruitment of signaling protein and regulating cell proliferation and differentiation. Claudin-4 is generally overexpressed in epithelial neoplasms.

 Staining patterns

• Membranous staining
• Cytoplasmic staining is considered non-specific

References

1. Oda T et al. Immunocytochemical utility of claudin-4 versus those of BerEP4 and MOC31 in effusion cytology. Diagnostic Cytopathology 2016 44(6):499- 504.
2. Facchetti F et al. Claudin 4 identified a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions Virchows Arc 2007;451:669-680.
3. Chauouche-Mazouni S et al. Claudin 3, 4, and 15 expression in solid tumors of lung adenocarcinoma versus malignant pleural mesothelioma. Annals of Diagnostic Pathology 2015 19(4):193-197.
4. Patel A et al. Utility of Claudin-4 versus BerEP4 and B72.3 in pleural fluids with metastatic adenocarcinoma. J Am Soc Cytopathol 2020;9(3):146-151.
5. Jo VY et al. Claudin 4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology. Cancer Cytopathol 2014;122:299-306.
6. Afshar-Moghaddam N et al. Diagnostic value of claudin-4 marker in pleural and peritoneal effusion cytology: Does it differentiate between metastatic adenocarcinoma and reactive mesothelial cells? Adv Biomed Res 2014;3:161.