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Tight Junction Proteins and Perineurial Cells in Neurofibromas

Kati P. Pummi, Heikki J. Aho, Matti K. Laato, Juha T.K. Peltonen and Sirkku A. Peltonen

Departments of Medical Biochemistry and Molecular Biology (KPP, MKL), Department of Dermatology (KPP,SAP), Department of Pathology (HJA), Department of Surgery (MKL), Department of Anatomy (JTKP), University of Turku, Turku, Finland, and Department of Anatomy and Cell Biology (JTKP) and Department of Dermatology (JTKP), University of Oulu, Oulu, Finland

Correspondence to: Sirkku Peltonen, Department of Dermatology, Turku University Hospital, PL 52 20521, Turku, Finland. E-mail: sirkku.peltonen{at}tyks.fi

Cutaneous neurofibromas consist of axonal processes, Schwann cells, fibroblasts, perineurial cells, mast cells, and abundant extracellular matrix. The distribution and role of perineurial cells in neurofibromas has been uncertain, partly because there has not been a specific immunohistochemical marker for perineurial cells. In this study, tight junctions (TJs) of 16 neurofibromas from 12 patients with neurofibromatosis type 1 (NF1) were analyzed using electron microscopy, immunohistochemistry, and Western transfer analysis. Cell–cell contacts with typical ultrastructural morphology of TJs were seen between adjacent perineurial cells surrounding the small nerves and between contacting perineurial cell processes embedded in tumor stroma. Immunohistochemistry showed expression of claudin-1, claudin-3, and ZO-1 in the intercellular junctions of a subpopulation of tumor cells. Occludin was present mainly in perineurium and claudin-5 localized to the blood vessels. Double immunolabelings were used to identify the cell types expressing claudin-1. The results showed that claudin-1 positive cells were also positive for type IV collagen and epithelial membrane antigen but not for S-100 protein. This labeling pattern is consistent with perineurial cell phenotype. Using claudin-1 as a marker, our results showed that clusters of perineurial cells are distributed around the rudimentary nerves within cutaneous neurofibromas and at the periphery of some neurofibromas. (J Histochem Cytochem 54:53–61, 2006)

Key Words: claudin-1 • epithelial membrane antigen • neurofibroma • neurofibromatosis • perineurial cell • Schwann cell • S-100 • tight junction • ZO-1

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