Anatomical Pathology Special Stains and Immunohistochemistry
RCPAQAP myQAP login Data Analysis

Claudin-4

Platform
Leica Bond-PRIME
Clone/manufacturer
3E2C1 (Invitrogen)
Antibody dilution
1:400
Antibody incubation time/temp
15 mins at 37°C
Antigen retrieval buffer time/temp
Leica ER2 40 mins at 100°C
Amplification
Not applicable
Detection kit
DS284 DAB Polymer Refine
Program (mark)
General 2025 (4.5/5)

Claudin-4 (Clostridium perfringens enterotoxin receptor) is a tight junction protein encoded by the gene CLDN4. Claudin-4 has been shown to distinguish adenocarcinoma from malignant mesothelioma with 99% specificity in malignant effusions (1). Basal-like tumours also demonstrated overexpression of Claudin-4 (2). Loss of Claudin-4 was also seen in 69% of advanced gastric cancers and correlated with poor differentiation (3).

Recommended Controls

The criteria for acceptable staining is membranous. The mesothelioma should be negative, normal lung and lung adenocarcinoma should demonstrate positive staining. The recommended controls to use is a positive (lung adenocarcinoma) and negative tumour (mesothelioma).

Expected staining pattern


Mesothelioma


Lung adenocarcinoma


Normal lung 1


Normal lung 2

Disclaimer

These methods are intended as a guide only. Laboratories that wish to implement these methods should perform internal validation/verification prior to use. The RCPAQAP does not make any claim or warranty for the accuracy or performance of these methods.

References
  1. Jo VY, Cibas ES, Pinkus GS. Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology. Cancer Cytopathol. 2014 Apr;122(4):299-306.

  2. Lanigan F, et al. Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer. Int J Cancer. 2009 May 1;124(9):2088-97.

  3. Kolokytha P, et al. Claudin-3 and claudin-4: distinct prognostic significance in triple-negative and luminal breast cancer. Appl Immunohistochem Mol Morphol. 2014;22(2):125-31.

  4. Images of mesothelioma, lung adenocarcinoma and normal lung_ QAP survey results

Last updated on February 27, 2026
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