Biologic correlates of a biochemoprevention trial in advanced upper aerodigestive tract premalignant lesions.
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.
Papadimitrakopoulou
Vassiliki A
VA
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. vpapadim@mdanderson.org
Liu
Diane D
DD
Mao
Li
L
Shin
Dong M
DM
El-Naggar
Adel
A
Ibarguen
Heladio
H
Lee
J Jack
JJ
Hong
Waun K
WK
Hittelman
Walter N
WN
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
D014408:Biomarkers, Tumor