title: Biologic correlates of a biochemoprevention trial in advanced upper aerodigestive tract premalignant lesions.
abstract: OBJECTIVE
  To identify tissue biomarkers that might be used to assess an individual's cancer risk and response to chemoprevention, we studied in dysplastic lesions of the larynx and the p.o. cavity, a series of biomarkers extensively used in previous chemoprevention trials, including chromosome polysomy (CP), proliferative status, p53 expression and gene mutations, and loss of heterozygosity at 9p, 3p, and 17p.
  
  
  METHODS
  Biopsies from 32 participants in a prospective chemoprevention trial using 13-cis-retinoic acid, IFN-alpha, and alpha-tocopherol for 12 months (20 with vocal cord and 12 with p.o. cavity lesions) were analyzed for p53 and Ki-67 expression by immunohistochemistry, loss of heterozygosity by PCR amplification, p53 mutations by PCR-based direct sequencing, and CP by in situ hybridization.
  
  
  RESULTS
  High CP (> or =4% cells with more than three chromosome copies per nucleus) was more common in p.o. (8 of 10) than laryngeal lesions (4 of 16; P = 0.01), and so was a combination of CP > or = 4% and parabasal layer p53 labeling index > or = 0.2 (P = 0.02). Low CP was a significant predictor of complete histological response (8 of 14 cases with low versus 1 of 12 cases with high CP; P = 0.01). A trend for histological progression or cancer development was observed in cases with high CP and parabasal layer p53 labeling index.
  
  
  CONCLUSIONS
  Low CP, more frequently observed in laryngeal lesions, appears to be a predictor of response to chemoprevention and could be used as a screening tool to identify suitable candidates for such approaches. Further investigation of biological parameters of response and cancer risk is warranted.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. vpapadim@mdanderson.org
authors.forename: Vassiliki A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Mao
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: Adel
authors.initials: A
authors.lastname: El-Naggar
authors.forename: Heladio
authors.initials: H
authors.lastname: Ibarguen
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Walter N
authors.initials: WN
authors.lastname: Hittelman
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D018890:Chemoprevention; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D005260:Female; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor