Keratin 15 (K15) is a type I keratin without a defined type II partner whose expression in epidermal diseases has not been investigated. In this study we have used LHK15, a monoclonal antibody raised against the last 17 amino acids of the K15 polypeptide, to show that K15 is expressed primarily in the basal keratinocytes of stratified tissues, including the fetal epidermis and fetal nail. Although K15 in normal hair follicles was virtually absent from hair bulbs, it was expressed by a subset of keratinocytes in the outer root sheath. By comparison, K14 expression was found throughout the outer root sheath of hair follicles; however, when both K14 alleles were naturally ablated, the expression of K15 was also observed throughout the outer root sheath of the follicles. Expression of K15 mRNA was assessed by in situ hybridization and corroborated the data from immunostaining. An increase in K15 mRNA and protein expression in hair follicles from the K14 ablated epidermis suggested an upregulation of the K15 gene in the absence of the K14 protein. In organotypical cultures where differentiating keratinocytes expressed markers of activated phenotype, i.e., K6 and K16, expression of K15 was undetectable. The expression of K15 mRNA and protein was also downregulated in two hyperproliferating situations, psoriasis and hypertrophic scars. Because keratinocytes in psoriasis and hypertrophic scars are activated, we conclude that K15 expression is not compatible with keratinocyte activation and the K15 gene is downregulated to maintain the activated phenotype.

Our data indicate that HIF-1alpha is upregulated at both protein and mRNA levels in OSF and the correlation with epithelial dysplasia is statistically significant (P < 0.001). We propose that HIF-1alpha may play a role in malignant transformation of OSF. Further, over-expression of HIF-1alpha may contribute to the progression of fibrosis. It may be possible to use HIF-1alpha as a marker for malignant transformation of OSF.

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.

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Background:UK oral cancer incidence has risen by 22% in the last 10 years. Oral cancer is often detected at a late stage when treatment is debilitating and the chances of survival are poor. Certain black and minority ethnic groups are at elevated risk of oral cancer due to the prevalence of risk factor behaviours. We describe the background to, the development of and outcomes of an oral cancer screening activity appropriate to the needs of members of a disadvantaged community at high risk of oral cancer, carried out between 2006 and 2008 in Tower Hamlets, East London.Methods:In all, 1320 people participated during 34 days of screening, divided into two phases (Phase I (2006/2007): n=485, Phase II (2008): n=835). Modifications to the delivery process were implemented for Phase II in an attempt to recruit more high-risk individuals and to improve screening specificity.Results:In total, 75 people were urgently referred for further investigation (Phase I: n=20, Phase II: n= 55). Nine were diagnosed with dysplastic lesions (Phase I: n=3, Phase II: n=6) and a further eight showed potentially malignant disorders without dysplasia (Phase I: n=1, Phase II: n=7). Screening participants with low levels of completed education (OR: 6.94, 95% CI: 1.66, 28.98) and who chewed paan with tobacco (OR: 8.01, 95% CI: 3.54, 18.08) were more likely to be referred for further investigation.Conclusion:The project offers insights for the further development of oral cancer screening interventions for disadvantaged communities.