title: Unusual remodeling of the hyalinization band in vulval lichen sclerosus by type V collagen and ECM 1 protein.
abstract: OBJECTIVE
  The vulva is the primary site affected in lichen sclerosus, a chronic dermatosis in women that is histologically characterized by a zone of collagen remodeling in the superior dermis. The normal physiological properties of the vulva depend on the assembly of collagen types I (COLI), III (COLIII) and V (COLV), which form heterotypic fibers, and extracellular matrix protein interactions. COLV regulates the heterotypic fiber diameter, and the preservation of its properties is important for maintaining normal tissue architecture and function. In the current work, we analyzed the expression of COLV and its relationship with COLI, COLIII, elastic fibers and extracellular matrix protein 1 in vulvar biopsies from patients with lichen sclerosus.
  
  
  METHODS
  Skin biopsies from 21 patients with lichen sclerosus, classified according to Hewitt histological criteria, were studied and compared to clinically normal vulvar tissue (N=21). Morphology, immunohistochemistry, immunofluorescence, 3D reconstruction and morphometric analysis of COLI, COLIII, COLV deposition, elastic fibers and extracellular matrix 1 expression in a zone of collagen remodeling in the superior dermis were performed.
  
  
  RESULTS
  A significant decrease of elastic fibers and extracellular matrix 1 protein was present in the hyalinization zone of lichen sclerosus compared to healthy controls. The non-homogeneous distribution of collagen fibers visualized under immunofluorescence in the hyalinization zone of lichen sclerosus and control skin was confirmed by histomorphometry. Lichen sclerosus dermis shows a significant increase of COLI, COLIII and COLV expression compared to the healthy controls. Significant inverse associations were found between elastic fibers and COLV and between COLV and extracellular matrix 1 expression. A direct association was found between elastic fiber content and extracellular matrix 1 expression. Tridimensional reconstruction of the heterotypic fibers of the lichen sclerosus zone of collagen remodeling confirmed the presence of densely clustered COLV.
  
  
  CONCLUSIONS
  Increased deposition of abnormal COLV and its correlation with extracellular matrix 1 and elastic fibers suggest that COLV may be a trigger in the pathogenesis of lichen sclerosus.
authors.affiliation: Department of Pathology, Faculdade de Medicina, São Paulo, SP, Brazil.
authors.forename: Charles A P
authors.initials: CA
authors.lastname: Godoy
authors.affiliation: Division of Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Walcy R
authors.initials: WR
authors.lastname: Teodoro
authors.affiliation: Division of Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Ana Paula P
authors.initials: AP
authors.lastname: Velosa
authors.affiliation: Department of Pathology, Faculdade de Medicina, São Paulo, SP, Brazil.
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Garippo
authors.affiliation: Department of Pathology, Faculdade de Medicina, São Paulo, SP, Brazil.
authors.forename: Esmeralda Miristeni
authors.initials: EM
authors.lastname: Eher
authors.affiliation: Department of Pathology, Faculdade de Medicina, São Paulo, SP, Brazil.
authors.forename: Edwin Roger
authors.initials: ER
authors.lastname: Parra
authors.affiliation: Department of Dermatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Mirian N
authors.initials: MN
authors.lastname: Sotto
authors.affiliation: Department of Pathology, Faculdade de Medicina, São Paulo, SP, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D000368:Aged; D001706:Biopsy; D003094:Collagen / Q000378:metabolism; D024062:Collagen Type V / Q000378:metabolism*; D004547:Elastic Tissue / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D006818:Hyalin / Q000378:metabolism*; D021621:Imaging, Three-Dimensional / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D014844:Vulva / Q000378:metabolism / Q000473:pathology; D007724:Vulvar Lichen Sclerosus / Q000378:metabolism* / Q000473:pathology
chemical_list: D024062:Collagen Type V; C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins; D003094:Collagen