title: Altered expression of the hemidesmosome-anchoring filament complex proteins in basal cell carcinoma: possible role in the origin of peritumoral lacunae.
abstract: Basal cell carcinoma (BCC) is a frequent skin cancer with low metastatic potential. Expression of the anchoring filament proteins, native laminin-5 and its individual alpha 3, beta 3 and gamma 2 chains, uncein. and linear IgA antigen was examined by immunostaining in 17 BCC with different histological subtypes. Immunoreactivity of the hemidesmosomal proteins, integrin alpha 6 beta 4, 230-kDa bullous pemphigoid antigen (BP-230 Ag) and plectin/HD-1, and that of dermal-epidermal junction (DEJ) components, integrin alpha 2 beta 1, laminin-1, collagen IV, and collagen VII was also analysed. Around tumour nests, the labelling of laminin-5 was absent or markedly reduced in 12 BCC (comprising eight solid BCC, three adenoid BCC and one keratotic BCC) and strong in five BCC (comprising three adenoid BCC, one keratotic BCC and one adenoid and keratotic BCC). Intriguingly, in tumour cells of 12 BCC including laminin-5 negative tumours, a cytoplasmic reactivity of the laminin gamma 2 chain was detected, but not that of the alpha 3 and beta 3 chains. In the basement membrane of the epidermis overlying tumour nests, the labelling of laminin-5 was always strong. Uncein, linear IgA disease antigen, and integrin alpha 6 beta 4 were absent in solid BCC and weakly expressed in adenoid or keratotic BCC. For plectin/HD-1 and BP-230 Ag, a cytoplasmic reactivity was detected in the majority of the tumour cells. The labelling of integrin alpha 2 beta 1, laminin-1, collagen IV and collagen VII indicated no alteration in the synthesis of these proteins. In peritumoral lacunae, immunoreactivity of hemidesmosome and anchoring filament proteins was absent, except for plectin/HD-1 on the tumour side and sometimes for laminin-5 on the stromal side, while laminin-1, collagen IV and collagen VII were detected on the stromal side. These findings suggest that the components of the hemidesmosome-anchoring filament complex are not synthetized or assembled properly in BCC, and that the alteration of these adhesion structures may be the cause of peritumoral lacunae.
authors.affiliation: Department of Dermatology, Hôpital Archetz, Nice, France.
authors.forename: P
authors.initials: P
authors.lastname: Bahadoran
authors.forename: C
authors.initials: C
authors.lastname: Perrin
authors.forename: D
authors.initials: D
authors.lastname: Aberdam
authors.forename: A
authors.initials: A
authors.lastname: Spadafora-Pisani
authors.forename: G
authors.initials: G
authors.lastname: Meneguzzi
authors.forename: J P
authors.initials: JP
authors.lastname: Ortonne
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D002352:Carrier Proteins; D003094:Collagen / Q000378:metabolism; D003598:Cytoskeletal Proteins; D003896:Desmosomes / Q000378:metabolism; D000071821:Dystonin; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D051190:Plectin; D012878:Skin Neoplasms / Q000378:metabolism*; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D007070:Immunoglobulin A; D007381:Intermediate Filament Proteins; D007797:Laminin; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D051190:Plectin; D000097805:Collagen Type XVII; C486268:DST protein, human; C495332:PLEC protein, human