Chromosome polysomy and histological characteristics in oral premalignant lesions

Head and neck tumorigenesis has been postulated to represent a multistep pr ocess driven by the accumulation of carcinogen-induced genetic changes thro ughout the exposed tissue field. To better explore this genetic instability process at the tissue level, 59 regions within 26 biopsy tissue specimens from individuals with oral leukoplakia have been subjected to chromosome 9 in situ hybridization analysis, and the degree of chromosome instability wa s related to known clinical/pathological parameters associated with tumor r isk. Whereas chromosome indices were similar between high-risk lesion sites and low-risk lesion sites, high-risk lesions showed higher levels of chrom osome polysomy than did low-risk sites [median PIs (polysomy indices), 2.1 versus 1.4, respectively], Similarly, dysplastic regions showed significant ly higher chromosome polysomy levels than hyperplastic regions (median PIs, 2.4 versus 1.5, respectively), Interestingly, however, hyperplastic region s in the same biopsy as dysplastic regions showed two-times higher polysomy levels than those in biopsies without dysplasia (median PIs, 2.6 versus 1. 3, respectively), suggesting that chromosome polysomy determinations provid e a field measurement for the degree of ongoing genetic insult. Finally, ch romosome polysomy tended to persist or increase in the superficial epitheli al layers in regions showing koilocytosis, whereas their frequency decrease d in nonkoilocytotic regions, suggesting that epigenetic factors may serve to perpetuate the levels of genetically unstable cells in the epithelium. T hese results provide direct support for the field cancerization process and suggest that measurements of genetic instability might provide additional biological information beyond histology and lesion site characteristics in the assessment of head and neck cancer risk.