p53-positive tumor-distant squamous epithelia of the head and neck reveal selective loss of chromosome 17.

ABSTRACT

OBJECTIVES/HYPOTHESIS: The progression of clinically manifest premalignant lesions in the head and neck region to primary or second primary cancer is characterized by numerical and structural chromosomal aberrations. However, many tumors arise from histologically inconspicuous mucosal sites. The objective was to investigate whether chromosomal aberrations can be detected in tumor-distant mucosa and whether they can help predict the risk of second primary malignancy. STUDY DESIGN: A retrospective series of 72 clinically healthy, arbitrarily taken mucosal samples from 53 patients with squamous cell carcinoma of the head and neck was studied. A previous analysis of the p53 protein status had revealed both p53-positive and p53-negative samples. METHODS: The samples were analyzed by fluorescence in situ hybridization (FISH) using centromeric probes specific for the chromosomes 1, 10, 17, and 18. RESULTS: Tumor-distant mucosa generally showed increased numerical chromosomal aberrations, which consisted mainly of monosomies. In the group of patients with p53-positive epithelia, all aberrations including gains of chromosomes (trisomies, tetrasomies) were more frequent. Monosomy for chromosome 17 was most significantly and selectively enhanced in this group (Wilcoxon Scores [rank sum] test, P =.0002). CONCLUSION: Detectable chromosomal aberrations occur in clinically healthy epithelia in patients at risk for secondary head and neck cancer. Specifically, unbalanced chromosome 17 monosomy in conjunction with p53 protein overexpression may constitute a valuable biomarker for progressive "field cancerization."