title: Expression of DNA damage response biomarkers during oral carcinogenesis.
abstract: Emerging evidence suggests that an intact DNA damage response (DDR) serves as a potent barrier to malignant transformation. Using immunohistochemistry and patient-derived biopsy samples, we investigated whether the same may hold true during oral carcinogenesis. DNA damage accumulates early in the development of oral squamous cell carcinoma (OSCC) as evidenced by the detection of surrogate DDR biomarkers γ-H2A.X and phosphorylated CHK2-threonine-68 (phospho-CHK2(Thr68)) in epithelial hyperplasias. However, whereas γ-H2A.X expression peaked in dysplastic epithelium, its levels were significantly reduced in OSCCs (χ(2) = 7.655; P = .02). In contrast, there was a trend toward increased phospho-CHK2(Thr68) expression with increasing severity of the pathology. Nonetheless, combined expression of the biomarkers was significantly greater in the nontransformed tissues relative to OSCCs (χ(2) = 6.42; P = .04). Thus, our findings suggest that early therapeutic exploitation of the DDR may be worthy of investigation as a means by which to limit OSCC development.
authors.affiliation: Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Shan-Ju
authors.initials: SJ
authors.lastname: Chou
authors.forename: Faizan
authors.initials: F
authors.lastname: Alawi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D004848:Epithelium / Q000473:pathology; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000032:analysis; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics*; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D013912:Threonine / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones; D010750:Phosphoproteins; D013912:Threonine; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases