title: Collagen XVII/BP180 protein expression in squamous cell carcinoma of the skin detected with novel monoclonal antibodies in archived tissues using tissue microarrays and digital microscopy.
abstract: Collagen XVII/BP180, a hemidesmosomal adhesion protein, is lost during normal keratinocyte maturation; however, it may be reexpressed upon malignant transformation. In this work, highly sensitive monoclonal antibodies 6D1 and 9G2 were produced, characterized, and used for the detection of collagen XVII in a tissue microarray series of archived samples of nonmelanocytic epithelial neoplasias, including 5 verruca vulgaris, 14 seborrheic keratosis, 38 actinic keratosis, 38 basal cell carcinoma (BCC), 15 basosquamous carcinoma, 58 squamous cell carcinoma (SCC), and 9 normal skin. Digital microscopy and a new tissue microarray software linking image and patient data allowed easy and validated evaluation and quality archiving of stained samples. In normal skin and benign epidermal lesions, collagen XVII protein was restricted to basal keratinocytes. However, possibly as a sign of undifferentiated/transformed state, it was widely expressed in SCC showing elevated levels around invasive tumor fronts with some staining in tumor adjacent stroma, endothelium, and histiocytes. Collagen XVII immunostaining of atypical keratinocytes in most actinic/solar keratosis supports the view of their malignancy and common origin with SCC. Squamous component of basosquamous carcinoma showed moderate reaction, whereas islets of BCC were mainly negative reflecting the diverse genotype and phenotype, and pathogenesis of SCC and BCC. These results suggest that collagen XVII neoexpression may be associated with early atypia/malignant transformation of keratinocytes. Further investigations are under way to analyze the potential of these antibodies for tracing progression and metastatic potential of skin tumors.
authors.affiliation: Laboratory of Tumor Pathology and Molecular Diagnostics, Bay Zoltan Foundation for Applied Research, University of Szeged, Szeged, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Stelkovics
authors.forename: Irma
authors.initials: I
authors.lastname: Korom
authors.forename: Ilona
authors.initials: I
authors.lastname: Marczinovits
authors.forename: Janos
authors.initials: J
authors.lastname: Molnar
authors.forename: Klara
authors.initials: K
authors.lastname: Rasky
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Raso
authors.forename: Levente
authors.initials: L
authors.lastname: Ficsor
authors.forename: Bela
authors.initials: B
authors.lastname: Molnar
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kopper
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenacs
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D002280:Basal Cell Carcinoma / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018715:Microscopy, Video / Q000295:instrumentation; D024041:Non-Fibrillar Collagens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D000097805:Collagen Type XVII
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D014408:Biomarkers, Tumor; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII