MALIGNANCY DETECTION BY MOLECULAR CYTOGENETICS IN CLINICALLY NORMAL MUCOSA ADJACENT TO HEAD AND NECK TUMORS

Objective: To identify the potential use of chromosome imbalances as b iomarkers for tumorigenesis in head and neck squamous cell carcinoma ( HNSCC) by fluorescence in situ hybridization (FISH). Design: In this c ase-control study, chromosome copy numbers were assessed in dual-targe t, dual-color FISH assays using DNA probes specific for 14 human chrom osomes (1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 15, 17, X, and Y) applied to exfoliated epithelial cells. Setting: University medical center. Patie nts: We examined 20 cell brushings (from 10 primary tumors and 10 clin ically normal margins) collected from 10 patients with HNSCC and compa red these with cell brushings from the oral cavity of 10 nonsmoker and 10 smoker control subjects. Intervention: None. Main Outcome Measure: Chromosomal aneuploidy. Results: Specimens from nonsmokers displayed greater than 91% of cells with normal; signals, indicating high analyt ical sensitivity for the probes. Specimens from smokers demonstrated l arge variability without significant imbalance (P>.05) compared with t hose from nonsmokers. Tumor specimens from patients with HNSCC display ed significant chromosomal imbalance (P<.05) for all probes except chr omosome Y. Similar imbalance, although in lower frequency, was found i n all clinically normal adjacent mucosa specimens. Conclusions: Interp hase FISH demonstrated great applicability in detecting chromosome imb alance associated with malignancy in HNSCC and clinically normal. adja cent cells, thereby detecting subclinical tumorigenesis. A panel of ch romosome probes (chromosomes 3, 8, 9, and 10) is proposed as an effici ent and sensitive additional tool for future routine screening of tumo r margins and potential diagnosis of residual diseasse in HNSCC.