| dc.description.abstract | Oral lichen planus (OLP) is a chronic mucocutaneous disease characterized by basal cell destruction and a subepithelial band-like mononuclear inflammatory cell infiltrate predominated by T cells. Molecular biological changes in the basal cell compartment and keratinocyte cell death have been a matter of particular interest in later OLP research. The majority of OLP lesions run a benign course. However, OLP have been associated with an increased risk of malignant transformation. The aims of this study were to investigate apoptotic cell death and putative regulatory proteins in keratinocytes (Papers I-III), as well as potential risk markers for malignant transformation in OLP (Paper III). Biopsies from clinically and histologically verified OLP were investigated (Papers I-II), as well as a biopsy material from OLP patients where a certain amount of them had developed epithelial dysplasia and oral squamous cell carcinoma (OSCC) (Paper III). Tissues were evaluated by histomorphometry, imunnohistochemistry (Papers I-III), TUNEL method (Paper I), mRNA in situ hybridization (Paper II) and image cytometry for measurement of DNA content (Paper III). Our data show that apoptosis is increased within the epithelium of OLP compared with normal oral mucosa (OM), and that both Fas receptor (FasR) and Fas-ligand (FasL) apoptosis regulatory proteins are expressed within the epithelium and subepithelial cell infiltrate of OLP (Paper I). In actively diseased OLP lesions, basal keratinocytes are CD40 negative and epithelial (E)-cadherin negative in focal areas (Papers II-III). Cyclooxygenase-2 (Cox-2) is up-regulated within the epithelium of OLP lesions, compared with normal OM (Paper III). According to DNA content measurements, all biopsies were classified as diploid including OLP, epithelial dysplasia and OSCC, except for one biopsy from an OLP lesion with epithelial dysplasia which was tetraploid (Paper III). Based on these findings we conclude that basal keratinocytes in OLP die by apoptosis and regulation of apoptosis appears to involve following mechanisms; (1) dysfunction in FasR/FasL system; (2) by down-regulating CD40 in diseased areas, basal keratinocytes may escape CD40-CD40L mediated apoptosis; (3) an up-regulation of Cox-2 , which may inhibit apoptosis; (4) loss of E-cadherin in basal keratinocytes may promote apoptosis and contribute to reduced basal cell structural integrity in OLP, allowing T cells to enter the epithelial compartment. Our biopsy material indicates that neither DNA content, nor expression of Cox-2 and E-cadherin are reliable as prognostic markers to select the OLP patients at risk for development of OSCC. | en_US |
