Background: Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of β‐ and γ‐catenins in blistering diseases. The objective of this study was to evaluate the role of β‐ and γ‐catenins in the pathogenesis of acantholysis in pemphigus vulgaris.

Methods: β‐ and γ‐catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients.

Results: Healthy skin and normal oral mucosa showed a strong β‐ and γ‐catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of γ‐catenin was detected in 28/30 cases, and in 19/30 cases of PV for β‐catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for β‐catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for γ‐catenin.

Conclusions: Abnormal distribution of γ‐catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. γ‐catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the β‐catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.