title: An altered keratinocyte phenotype in oral submucous fibrosis: correlation of keratin K17 expression with disease severity.
abstract: Oral submucous fibrosis (OSF) is characterized by abnormal collagen metabolism in the submucosal connective tissue. Its influence on the overlying epithelium is not known but about 14% of OSF cases undergo malignant transformation to squamous cell carcinoma indicating association with abnormality of the epithelium. Here, we have defined the keratin expression profile, by immunohistochemistry and quantitative image analysis, using a panel of 22 anti-keratin monoclonal antibodies on 28 OSF samples. We observed an increase of K1 and K10 in the suprabasal layers, induction of K6 in the basal layer and complete loss of K19 in the epithelium. Furthermore, there was increased K17 expression in the suprabasal layers, which correlated with disease severity. In a subset of the most severe OSF cases (14%), K17 expression was completely lost in the basal layer which might define them to be at most risk to undergo malignant transformation. There was no detectable expression of K8, K18, K7 and K9 and the expression of K4, K13, K14, K15 and K16 did not change in OSF. We propose that the altered keratin profiles could be useful as histological diagnostic markers and provide important insights into the pathogenesis of the disease and its predisposition to malignancy.
authors.affiliation: Programme in Muco-Cutaneous Oncology, Centre for Clinical and Diagnostic Oral Sciences, Institute of Cell and Molecular Sciences, London, UK.
authors.forename: Anand
authors.initials: A
authors.lastname: Lalli
authors.forename: Wanninayake M
authors.initials: WM
authors.lastname: Tilakaratne
authors.forename: Anura
authors.initials: A
authors.lastname: Ariyawardana
authors.forename: Caroline
authors.initials: C
authors.lastname: Fitchett
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Eleni
authors.initials: E
authors.lastname: Hagi-Pavli
authors.forename: Alan T
authors.initials: AT
authors.lastname: Cruchley
authors.forename: E Kenneth
authors.initials: EK
authors.lastname: Parkinson
authors.forename: Muy-Teck
authors.initials: MT
authors.lastname: Teh
authors.forename: Farida
authors.initials: F
authors.lastname: Fortune
authors.forename: Ahmad
authors.initials: A
authors.lastname: Waseem
mesh_terms: D015415:Biomarkers; D002294:Carcinoma, Squamous Cell; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053537:Keratin-17 / Q000096:biosynthesis; D015603:Keratinocytes / Q000737:chemistry / Q000473:pathology*; D007633:Keratins / Q000096:biosynthesis* / Q000235:genetics; D009062:Mouth Neoplasms / Q000737:chemistry / Q000473:pathology; D009914:Oral Submucous Fibrosis / Q000473:pathology*; D010641:Phenotype; D023861:Photography, Dental; D011230:Precancerous Conditions / Q000737:chemistry / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D053537:Keratin-17; D007633:Keratins