APOPTOSIS-ASSOCIATED MARKERS IN ORAL LICHEN-PLANUS

Hypothesizing that loss of basal cells in oral lichen planus is due to apoptosis, we evaluated LP specimens for apoptosis-regulating protein s [positive regulators Bcl-x(s), Bax, Fas/Fas-ligand, p53, and negativ e regulators (anti-apoptotic) Bcl-2, Bcl-x(L)] and compared results wi th reactions in normal mucosa and chronically inflamed gingiva. Also, sections were evaluated with an in situ TUNEL assay that identifies ap optotic DNA fragments. Basal keratinocytes in normal buccal mucosa, no nspecific gingivitis, and LP were negative for Bcl-2 protein, but mela nocytes and lymphoid cells were positive. Keratinocyte staining for Bc l-x was negative to weak in normal buccal mucosa and gingivitis, and m oderate in LP. Keratinocytes (especially upper prickle cells) in all t issues stained similarly for Bax at weak to moderate levels. Also, no differences In Fas and Fas-ligand staining were evident. Prominent p53 -positive staining was seen in all LP biopsies (10-100% of basal kerat inocytes) but not in normal buccal mucosa and gingivitis. Few basal ke ratinocytes in 5/10 LP cases exhibited a positive in situ signal for D NA fragment-associated apoptosis. That the Bcl-2 family of proteins an d Fas/Fas-ligand were detected in normal and diseased tissues, and wer e occasionally expressed differently in oral LP, supports the notion t hat apoptosis is a potential mechanism of keratinocyte loss, especiall y in LP. The pattern of p53 staining in oral LP suggests over-expressi on of wild-type protein a phenomenon that would arrest the cell cycle to allow repair of damaged DNA, or trigger apoptosis. While immunohist ochemical evidence for apoptosis-associated basal keratinocyte death i n LP was slight, it appeared that it may be p53 protein, and possibly Bcl-x, associated.