J Cutan Pathol 2002: 29: 540–548 Copyright C Blackwell Munksgaard 2002 Blackwell Munksgaard . Printed in Denmark Journal of Cutaneous Pathology ISSN 0303-6987 Strict correlation between uPAR and plakoglobin expression in pemphigus vulgaris Background: Recent studies have reported nuclear delocalization Lorenzo Lo Muzio 1 , of plakoglobin in acantholytic pemphigus vulgaris cells. The Giuseppe Pannone 2 , objective of this study was to evaluate the role of plakoglobin in the Stefania Staibano 2 , pathogenesis of acantholysis in pemphigus vulgaris (PV) and its Michele Davide Mignogna 3 , relation with the urokinase-type plasminogen activator receptor Corrado Rubini 4 , (uPAR) expression. Giampietro Farronato 5 , Materials and methods: Plakoglobin and uPAR expressions were Francesca Ferrari 6 , evaluated by immunohistochemistry in 22 cases of PV at various Pier Francesco Nocini 6 and stages of the disease, and as controls in 18 specimens of skin/oral Gaetano De Rosa 2 mucosa from healthy patients. 1 Institute of Dental Sciences, University of Results: Healthy skin/normal oral mucosa showed strong Ancona, Ancona, 2 Department of Biomorphological and Functional Sciences, plakoglobin expression in the basal and spinous layers with prevalent Pathology Unit and 3 Department of Dental cellular membrane distribution; the intensity of staining progressively Sciences, University of Naples Federico II, decreased toward the superficial layers of the epithelium. In PV Naples, 4 Institute of Pathological Anatomy, patients, a progressive displacement of the plakoglobin signal toward University of Ancona, Ancona, 5 Institute of the nucleus was found in 18/22 of the cases. Healthy skin/normal oral Clinical Dentistry, University of Milano, Milano, and 6 Division of Maxillo-facial Surgery, mucosa showed low uPAR expression with prevalent cellular University of Verona, Verona, Italy membrane distribution. In the PV patients, strong uPAR expression was present in the acantholytic cells in 16/22 of the cases. There was direct correlation (p  0.05) between the uPAR expression and nuclear plakoglobin. Conclusions: The uPAR overexpression in acantholytic PV may be considered a direct consequence of plakoglobin abnormal distribution. Nuclear delocalization of plakoglobin, a direct consequence of plakoglobin-Dsg-3 dissociation induced by PV IgG, probably induces uPAR overexpression. This evidence suggests a central role for plakoglobin in PV pathogenesis because of its delocalization toward the nucleus, which is the probable cause of the uPAR gene expression. Prof. Lorenzo Lo Muzio MD, DMD, PhD, Via Carelli 28–71100, Foggia, Italy Lo Muzio L, Pannone G, Staibano S, Mignogna MD, Rubini C, Tel/Fax: π39 0881 685809 Farronato G, Ferrari F, Nocini PF, De Rosa G. Strict correlation E-mail: lomuziol/tin.it between uPAR and plakoglobin expression in pemphigus vulgaris. J Cutan Pathol 2002; 29: 540–548. C Blackwell Munksgaard 2002. Accepted 8 April, 2002 Autoantibodies to desmosomes’ components induce pemphigus vulgaris (PV), a rare autoimmune blis- tering disease of the skin and mucosae. 1,2 The lesion results from the loss of keratinocyte cohesion in the suprabasal area of the epithelia. 3,4 Desmoglein-3 (Dsg-3), a protein of 130 kDa local- ized at desmosomal regions, 5–9 is the target antigen 540 in PV. Desmosomes, highly organized intercellular junctions, are composed of two types of proteins: 1 (i) transmembrane proteins, such as desmoglein and desmocollin, which mediate cell-cell adhesion, 2 and (ii) intracytoplasmic plaque proteins, such as desmo- plakins 10,11 and plakoglobin, 12 which are involved in the association of the desmosomal complex with the