title: Expression of Bak and Bak/Mcl-1 ratio can predict photodynamic therapy outcome for oral verrucous hyperplasia and leukoplakia.
abstract: BACKGROUND
  Our previous studies showed that topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is very effective for oral verrucous hyperplasia (OVH) and relatively less effective for oral leukoplakia (OL) lesions. Nevertheless, there has been no report on the association of the expression of apoptosis-related proteins in OVH and OL biopsy tissues prior to PDT with PDT treatment outcomes.
  
  
  METHODS
  This study used immunohistochemistry to evaluate whether the expression of Bak, Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, or PCNA protein in biopsy specimens of OVH and OL lesions could be used to predict the clinical outcomes of 18 OVH and 40 OL lesions treated with topical ALA-PDT. The marker labeling score (LS) was defined as labeling index (positive cells/total cells) multiplied by staining intensity. The lesions after ALA-PDT treatment were divided into complete response (CR) group and partial or no response (PR/NR) group.
  
  
  RESULTS
  The mean Bak LS and the mean Bak/Mcl-1 LS ratio were significantly higher in the CR group than in the PR/NR group. However, there was no significant difference in the Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, or PCNA protein LS between the CR and PR/NR groups.
  
  
  CONCLUSIONS
  We conclude that the Bak LS or Bak/Mcl-1 LS ratio may be a useful biomarker to predict the clinical outcomes of OVH and OL lesions treated with topical ALA-PDT. Pre-PDT epithelial cell levels of Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, and PCNA may not have a significant influence on the clinical outcome of OVH and OL lesions treated with topical ALA-PDT.
authors.affiliation: School of Dentistry, College of Oral Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chuan-Hang
authors.initials: CH
authors.lastname: Yu
authors.forename: Hsin-Ming
authors.initials: HM
authors.lastname: Chen
authors.forename: Hung-Pin
authors.initials: HP
authors.lastname: Lin
authors.forename: Chun-Pin
authors.initials: CP
authors.lastname: Chiang
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D053148:Caspase 3 / Q000032:analysis; D053181:Caspase 8 / Q000032:analysis; D053453:Caspase 9 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007633:Keratins / Q000032:analysis; D007972:Leukoplakia, Oral / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012074:Remission Induction; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D055815:Young Adult; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000032:analysis*
chemical_list: C494772:BAK1 protein, human; D015415:Biomarkers; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D017319:Photosensitizing Agents; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D007633:Keratins; D000622:Aminolevulinic Acid; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9