Inactivation of Human MutL Homolog 1 and MutS Homolog 2 Genes in Head and Neck Squamous Cell Carcinoma Tumors and Leukoplakia Samples by Promoter Hypermethylation and Its Relation With

BACKGROUND. A subset of head and neck squamous cell carcinoma (HNSCC) exhibits a microsatellite instability (MIN) phenotype. The authors correlated alterations in the mismatch-repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2) in primary head and neck squamous cell carci-noma (HNSCC) tumors and in samples of leukoplakia with the MIN phenotype. METHODS. One hundred twenty-three paired HNSCC normal and tumor tissues and 27 leukoplakia samples were examined for hypermethylation of hMLH1 and hMSH2 promoters. The hypermethylation status of the tissues was confirmed by expression studies. Sixty-three of 123 randomly selected tumors and all 27 leuk-plakia samples were genotyped with 8 microsatellite markers to determine MIN. RESULTS. Fifty percent of HNSCC tumors and 63 % of leukoplakia samples har-bored hypermethylation at either or both hMLH1 and hMSH2 promoters. Normal tissues adjacent to methylation-positive tumors also demonstrated hypermethyl-ation of both promoters at a high frequency (25%). A positive correlation between tobacco habit and promoter hypermethylation was observed (P .001)