title: Caspase-3 expression is reduced, in the absence of cleavage, in terminally differentiated normal oral epithelium but is increased in oral squamous cell carcinomas and correlates with tumour stage.
abstract: Oral carcinomas are known to have a greater apoptotic index than normal oral epithelium, evident as shrinking cells with condensed chromatin. In this study, these morphologically apoptotic cells stained positively for cleaved (active) caspase-3. In normal oral epithelium, cleaved caspase-3 positive-cells were only rarely detected. The terminally differentiated surface epithelial layers did not express cleaved caspase-3. The caspase-3 pro-enzyme showed a gradient of expression in normal oral epithelium, decreasing with differentiation. No expression was detectable in surface epithelial layers. Lack of expression of the major 'executioner' caspase-3 may, at least in part, explain differences in morphology between terminally differentiated and apoptotic cells. In cancers of different tissue origins, caspase-3 pro-enzyme expression can be either increased or decreased compared with normal tissue counterparts. To determine how caspase-3 expression alters during oral carcinogenesis, caspase-3 expression was compared in 39 samples of normal oral epithelium and 54 oral squamous cell carcinomas. Squamous cell carcinomas had more intense caspase-3 staining than normal epithelium (p < 0.001). Moreover, within the oral squamous cell carcinoma series, there was significantly more intense nuclear and cytoplasmic staining with increasing STNMP stage (p = 0.017 and 0.03, respectively). This was a reflection of significant associations with site (S), palpable lymph nodes (N), and differentiation (P). Both caspase-3 staining intensity and the percentage of cells positive for caspase-3 were inversely associated with differentiation. Studies of the mechanisms by which high levels of caspase-3 expression are tolerated in oral carcinoma cells may identify targets that can be used to harness caspase-3 overexpression for therapeutic benefit.
authors.affiliation: Department of Oral and Dental Science, University of Bristol Dental School, Lower Maudlin Street, Bristol, BS1 2LY, UK. a.hague@bristol.ac.uk
authors.forename: Angela
authors.initials: A
authors.lastname: Hague
authors.forename: John W
authors.initials: JW
authors.lastname: Eveson
authors.forename: Marion
authors.initials: M
authors.lastname: MacFarlane
authors.forename: Suzanne
authors.initials: S
authors.lastname: Huntley
authors.forename: Nari
authors.initials: N
authors.lastname: Janghra
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004792:Enzyme Precursors / Q000032:analysis; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging
chemical_list: D004792:Enzyme Precursors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases