Astrocytoma ; genetics ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Frizzled Receptors ; genetics ; metabolism ; Glioblastoma ; genetics ; metabolism ; Glioma ; genetics ; metabolism ; Humans ; Paraffin Embedding ; RNA, Messenger ; metabolism ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; Wnt2 Protein ; genetics ; metabolism ; beta Catenin ; genetics ; metabolism

OBJECTIVETo study the role of abnormally activated Wnt/β-catenin signal pathway in the pathogenesis of scleroderma (SD) and its association with the clinical classification of SD.

METHODSThe expression and distribution of Wnt 2, Wnt 3a, and β-catenin in the skin lesions of 45 SD patients, including 25 with systemic sclerosis (SSc) and 20 with localized scleroderma (LSc), were detected with SP immunohistochemistry, using 20 samples from healthy skin tissues as normal control.

RESULTSIn the dermis and epidermis of the SD skin lesions, Wnt 2 and Wnt 3a were located in the cytoplasm and cell nuclei, respectively; β-catenin was distributed in the nuclei of dermal fibroblast-like cells, glandular epithelium cells and infiltrating lymphocytes, and on the cell membrane in normal and a part of the affected epidermis. The skin lesions of SD patients showed obviously increased staining intensity of cytoplasmic Wnt 2, nuclear Wnt 3a and β-catenin, but markedly lowered cell membrane staining of β-catenin than normal skins (P<0.01). Both Wnt 2 and Wnt 3a were positively correlated with nuclear β-catenin deposition (r=0.663 and 0.654, P<0.01) and negatively with cell membrane β-catenin staining (r=-0.532 and -0.529, P<0.01). No significant difference was found in the staining intensities of the 3 proteins between SSc and LSc (P>0.05).

CONCLUSIONAbnormal activation of Wnt/β-catenin pathway occurs in the skin lesions of SD patients, which may play an important role in the pathogenesis of SD. SSc and LSc represent the two opposite ends of the SD spectrum rather than two separate diseases.

Adolescent ; Adult ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Scleroderma, Systemic ; metabolism ; pathology ; Signal Transduction ; Skin ; pathology ; Wnt Signaling Pathway ; Wnt2 Protein ; metabolism ; Wnt3A Protein ; metabolism ; Young Adult ; beta Catenin ; metabolism