title: Sequential increases in proliferating cell nuclear antigen expression in head and neck tumorigenesis: a potential biomarker.
abstract: BACKGROUND
  Proliferating cell nuclear antigen (PCNA) is a 36-kd nuclear protein whose expression is associated with DNA synthesis and cell proliferation. Tumorigenesis in head and neck squamous cell carcinoma is proposed to be a multistep process; dysregulation of proliferation is a potential marker of this process.
  
  
  OBJECTIVE
  PCNA dysregulation was analyzed in squamous cell carcinoma tissue samples containing premalignant lesions (hyperplasia and/or dysplasia) and in adjacent normal epithelium to better understand proliferative changes during head and neck tumor development.
  
  
  METHODS
  Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded sections by using a monoclonal anti-PCNA antibody. PCNA expression was analyzed in 33 head and neck squamous cell carcinomas and in their adjacent premalignant lesions from different sites and compared with that in the control samples, which had never been exposed to first-hand tobacco smoke. PCNA expression was assessed by semiquantitative scoring (scale 0-3) in three epithelial layers (basal, parabasal, and superficial). The labeling index and the weighted mean index of PCNA expression were calculated.
  
  
  RESULTS
  Normal epithelium adjacent to the tumor had much more proliferative activity than the controls: The weighted mean index of PCNA expression was four-fold higher in the basal layer and sixfold higher in the parabasal layer. PCNA expression increased as tissues progressed from adjacent normal epithelium to hyperplasia (P < .001), hyperplasia to dysplasia (P < .001), and dysplasia to squamous cell carcinoma (P = .065); the total increase in PCNA expression ranged from fourfold to 10-fold from adjacent normal epithelium to squamous cell carcinoma. PCNA expression was higher in the parabasal than in the basal layer at all premalignant stages (23 of 25 samples in adjacent normal epithelium, 12 of 13 in hyperplasia, and 17 of 22 in dysplasia). As the tissue progressed from normal through premalignant stages to squamous cell carcinomas, we observed not only incremental increases in the labeling index, but also incremental increases in PCNA expression per labeled cells.
  
  
  CONCLUSIONS
  These results indicate that PCNA could be a useful biomarker for multistep carcinogenesis in head and neck cancer and may serve as an intermediate end point in chemopreventive trials.
authors.affiliation: Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: D M
authors.initials: DM
authors.lastname: Shin
authors.forename: N
authors.initials: N
authors.lastname: Voravud
authors.forename: J Y
authors.initials: JY
authors.lastname: Ro
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
authors.forename: W N
authors.initials: WN
authors.lastname: Hittelman
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D018809:Proliferating Cell Nuclear Antigen
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen