Abstract

Objective The identification of stem cells (SC) remains challenging. In the human oral mucosal epithelium, these cells are believed to be in the basal layer (stem cell niche), but their exact location is unclear. The aim of this study was to examine the dysplastic oral epithelium for these SC-like proteins in order to assess their diagnostic value as biomarkers complementing the histological grading of dysplasia.Material and Methods Thirty oral epithelial dysplasia (OED), 25 oral lichen planus (OLP), 10 oral hyperkeratosis and 5 normal oral epithelium (OE) were immunohistochemically examined for four SC markers [integrin β1, neuron-glial-2 (NG2), notch 1 (N1) and keratin 15 (K15)].Results Three of four SC markers were heterogeneously detected in all samples. K15 overexpression in the lower two-thirds of severe OED suggests an expanded SC niche. Integrin β1 distribution pattern was not measurably different between OEDs and control. NG2 was almost negative to absent in all samples examined. N1 expression was weak and highly variable in normal and dysplastic epithelium, making it an unreliable epithelial stem cell marker.Conclusions Present findings suggest that these markers were unable to identify individual epithelial stem cells. Instead, subpopulations of cells, most probably stem cells and transit amplifying cells with stem cell-like properties were identified in the dysplastic oral epithelium. The characteristic expressions of K15 might be of diagnostic value for oral dysplasia and should be investigated further.

Highlights

  • Stem cells constitute a distinct subset of cells characterized by their capacity to self-renewal and differentiation into multi-lineage cellular constituents of a specific tissue or organ25

  • The justification for choosing these four markers are: i) integrin β1, a component of integrin complexes, is expressed in high levels by epithelial stem cells13,14, ii) NG2, a chondroitin sulfate proteoglycan, is expressed by stem cells associated with interfollicular epidermis and hair follicles15, iii) notch 1 (N1) signaling is a direct determinant of stem cell fate in keratinocytes27, and iv) keratin 15 (K15), an intermediate filament protein is expressed in hair follicle bulge stem cells20

  • Among the four stem celllike protein markers evaluated, integrin β1 was the most widely expressed in both test and control samples, being detected mainly in the basal layer

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Summary

INTRODUCTION

Stem cells constitute a distinct subset of cells characterized by their capacity to self-renewal and differentiation into multi-lineage cellular constituents of a specific tissue or organ. The phenotypic characteristics of these cells are not fully realized, their morphological features include small size, poor differentiation and primitive cytoplasm. A reliable marker is necessary to characterize these cells, and putative stem cell markers need to be assessed for their differential specificities in identifying this cellular subset. Surrogate markers including keratins 15 and 19, integrins α6 and β1, and p63 are highly expressed by the epidermal stem cells and early progenitor cells. The aim of this study was to determine the differential expression of four stem cell markers, namely integrin beta 1 (β1), neuron-glial-2 (NG2), keratin 15 (K15) and notch 1 (N1) in the three constitutive tissue layers of dysplastic oral epithelium and compare their expression patterns with those of oral lichen planus (OLP), oral hyperkeratosis (OHK) and normal oral mucosa (NOM). The justification for choosing these four markers are: i) integrin β1, a component of integrin complexes, is expressed in high levels by epithelial stem cells, ii) NG2, a chondroitin sulfate proteoglycan, is expressed by stem cells associated with interfollicular epidermis and hair follicles, iii) N1 signaling is a direct determinant of stem cell fate in keratinocytes, and iv) K15, an intermediate filament protein is expressed in hair follicle bulge stem cells

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