Molecular support for field cancerization in the head and neck

BACKGROUND: Two competing concepts, field cancerization and micrometastatic lesions, have been postulated to account for the high frequency of second primary tumors and multicentric dysplasia in patients with head and neck carcinoma. METHODS: To provide insight into this process, the authors examined histologically normal mucosa and dysplastic tissue adjacent to invasive tumor for loss of heterozygosity (LOH) at three commonly deleted loci. Tissues from 21 patients with carcinoma of the oral cavity and oropharynx were identified and verified by a pathologist to contain histologically normal mucosa, dysplasia, and adjacent invasive squamous cell carcinoma. Each specimen was analyzed for LOH at D9S171 (9p21), D3S1007 (3p21.3-22), and D3S1228 (3p14). RESULTS: Of the 21 patients, 19 had adequate DNA for analysis. Seventeen patients were heterozygous at one or both of the 3p sites and LOH occurred in 6 of 17 invasive tumor specimens, 1 of 17 dysplasia specimens, and in none of the mucosal specimens. LOH at 9p21 occurred in 11 of 13 informative specimens of invasive tumor, 8 of 13 dysplasia specimens, and 6 of 13 normal mucosa specimens. However, one case that did not have 9p deletion in the tumor demonstrated LOH in the mucosa and two cases had LOH in both the tumor and mucosa but with deletion of the opposite allele. CONCLUSIONS: These data suggest that 9p21 but not 3p14 or 3p21 deletions occur in the absence of histologic changes. In two cases preinvasive and invasive lesions that apparently were an example of histologic progression contained disparate genetic events, calling into question the use of adjacent dysplasia as a model for premalignant lesions.