Diagnostic potential of Type VII Collagen during oral carcinogenesis

Abstract Type VII collagen (Col7) is a major component of anchoring fibrils. Col7 plays a role in tumor development and aggressiveness of cutaneous squamous cell carcinoma of recessive dystrophic epidermolysis bullosa. However, the role of Col7 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) remains largely unknown. Objective To elucidate the role of Col7 and its diagnostic potential during oral carcinogenesis. Methodology Col7 expression was immunohistochemically studied in 254 samples, including normal oral mucosa (NM), OL without dysplasia, OL with dysplasia, and OSCC. The correlation between Col7 expression and clinicopathologic parameters of OSCC was also determined. Results Col7 was present as a linear deposit at the basement membrane of NM, OL without dysplasia and OL with dysplasia, and at the tumor-stromal junction around tumor islands in OSCC. Discontinuity of expression was frequently observed in OL with dysplasia and OSCC. OSCC had the significantly lowest Col7 expression (p<0.0001). Compared with OL without dysplasia, OL with dysplasia showed significantly reduced Col7 expression. Patients in clinical stage 4 with positive nodes had low Col7 expression compared with those in clinical stage 1 and negative nodes, respectively. Conclusion Loss of Col7 is associated with tumorigenesis and aggressiveness in OSCC. A significantly reduced Col7 expression in OSCC implies that Col7 may be a useful marker for diagnosis and therapeutic targets.

Lúpus eritematoso sistêmico bolhoso: diagnóstico diferencial com dermatite herpetiforme / Bullous systemic lupus erythematosus: differential diagnosis with dermatitis herpetiformis

O lúpus eritematoso sistêmico bolhoso é um subtipo raro do lúpus eritematoso sistêmico, que ocorre ainda de forma mais incomum nos pacientes pediátricos. Relatamos o caso de uma adolescente de 12 anos, apresentando lesões vésico-bolhosas em face, pescoço, tronco, mucosas oral e genital, anemia, leucocitúria estéril, FAN: 1/1280 padrão nuclear pontilhado grosso, Anti-Sm e Anti-RNP positivos. O estudo anatomopatológico sugere dermatite herpetiforme e a imunofluorescência direta revela IgG, IgA e fibrina ao longo da zona de membrana basal. Apresentamos um caso típico de lúpus eritematoso sistêmico bolhoso e enfatizamos a importância do diagnóstico diferencial com a dermatite herpetiforme.

Bullous systemic lupus erythematosus is a rare subset of systemic lupus erythematosus that is even rarer in pediatric patients. We report a case of a 12-year-old girl who presented with a vesiculobullous eruption on her face, neck, trunk and genital and oral mucosa, as well as anemia, sterile pyuria, ANA (1:1280, speckled pattern) and positive anti-Sm and anti-RNP. Pathological examination suggested dermatitis herpetiformis, and direct immunofluorescence revealed IgG, IgA and fibrin in the epithelial basement membrane zone. We present a typical case of bullous systemic lupus erythematosus and emphasize the importance of clinical and histopathological differential diagnosis with dermatitis herpetiformis.

An Ultrastructural Examination of the Epitope Expression at Each Domain of Type VII Collagen in Patients with Epidermolysis Bullosa Acquisita / 대한피부과학회지

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an autoimmune disease characterized by circulating IgG autoantibodies which bind to the type VII collagen (C-VII). The major antigenic epitopes in C-VII, to which most EBA autoantibodies react, have been considered to be present in the N-terminal noncollagenous (NC1) domain. However, a novel EBA subgroup was recently identified with circulating antibodies, which target domain(s) other than or along with the NC1 domain of C-VII. These data suggest that there might be some heterogeneity in the autoantibody specificity to bind the domain-oriented epitopes in EBA. OBJECTIVE: The purpose of this study was to determine whether additional or independent epitopes exist in the C- terminal noncollagenous (NC2) and/or collagenous triple-helical (CTH) domain among Korean patients with EBA. METHODS: For this investigation, postembedding, indirect, immunogold electron microscopy was performed with the sera from 10 cases of EBA, having circulating autoantibodies against C-VII. The identification of the epitope and the relevant domain in each case were determined by ultrastructural localization of the immunogold particles. RESULTS: From 10 sera examined, all 10 cases showed deposits of gold particles confined to the area along the lamina densa (LD), without any other pattern of deposition. There was no case which revealed any independent/distinct deposits of the gold particles in the dermis below the LD. The ultrastructural locations of each domain (NC1, on the LD; NC2, 300~360 nm below the LD; CTH, between the area of NC1 and NC2) indicated that the epitopes recognized in all 10 Korean cases of EBA were expressed at the NC1 domain of C-VII. We did not find any additional or independent epitope in other domain. CONCLUSION: The results suggest that there may not be a wide heterogeneity in the domain-oriented topographic expression of antigenic epitopes in EBA; it is highly likely that the major epitopes present in Korean EBA cases reside within the NC1 domain of C7, similar to those observed with white population.

Immunogold Localization of Type VII Collagen in the Adhesion Complex of Pathologic Cornea

Type VII collagen is one of the major structural components of the corneal epithelial adhesion complex. Using the immunogold technique combined with indirect immunofluorescence analysis, the fine structural distribution of type VII collagen was studied in the corneas obtained from 5 enucleated hyman eyes (age range, 1-77 years) including one pathologic cornea from graft rejection. The findings on normal cornea corroborated the results from previous studies. In pathologic cornea from graft rejection, type VII collagen antibodies generated linear and irregular patchy fluorescence staining along the epithelial-stromal interface and immunogold binding to type VII collagen mainly occurred within the undulating lamina densa, more densealy distributed anchoring plaques and anchoring fibrils. The distribution of type VII collagen in pathologic human cornea from graft rejection is similar to normal human cornea. But, in pathologic cornea, type VII collagen is more densely distributed in superficial stroma and forms more extended anchoring network, which may be derived from the increased secretion of the type VII collagen due to the activated basal epithelial cell during healing process.