title: Apoptosis-associated markers in oral lichen planus.
abstract: Hypothesizing that loss of basal cells in oral lichen planus is due to apoptosis, we evaluated LP specimens for apoptosis-regulating proteins [positive regulators Bcl-xS, Bax, Fas/Fas-ligand, p53, and negative regulators (anti-apoptotic) Bcl-2, Bcl-xL and compared results with reactions in normal mucosa and chronically inflamed gingiva. Also, sections were evaluated with an in situ TUNEL assay that identifies apoptotic DNA fragments. Basal keratinocytes in normal buccal mucosa, nonspecific gingivitis, and LP were negative for Bcl-2 protein, but melanocytes and lymphoid cells were positive. Keratinocyte staining for Bcl-x was negative to weak in normal buccal mucosa and gingivitis, and moderate in LP. Keratinocytes (especially upper prickle cells) in all tissues 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 keratinocytes) but not in normal buccal mucosa and gingivitis. Few basal keratinocytes in 5/10 LP cases exhibited a positive in situ signal for DNA fragment-associated apoptosis. That the Bcl-2 family of proteins and Fas/Fas-ligand were detected in normal and diseased tissues, and were occasionally expressed differently in oral LP, supports the notion that apoptosis is a potential mechanism of keratinocyte loss, especially in LP. The pattern of p53 staining in oral LP suggests over-expression of wild-type protein; a phenomenon that would arrest the cell cycle to allow repair of damaged DNA, or trigger apoptosis. While immunohistochemical evidence for apoptosis-associated basal keratinocyte death in LP was slight, it appeared that it may be p53 protein, and possibly Bcl-x associated.
authors.affiliation: Department of Stomatology, School of Dentistry, University of California, San Francisco, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Dekker
authors.forename: F
authors.initials: F
authors.lastname: Lozada-Nur
authors.forename: L A
authors.initials: LA
authors.lastname: Lagenaur
authors.forename: L A
authors.initials: LA
authors.lastname: MacPhail
authors.forename: C Y
authors.initials: CY
authors.lastname: Bloom
authors.forename: J A
authors.initials: JA
authors.lastname: Regezi
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D002455:Cell Division; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000737:chemistry; D017676:Lichen Planus, Oral / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013194:Staining and Labeling / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000032:analysis
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D003856:Deoxyuracil Nucleotides; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor