Chromosome instability as an indicator of malignant progression in laryngeal mucosa

Purpose: Routine histologic examination cannot predict whether premalignant laryngeal lesions will progress toward invasive growth. The acquisition of changes in chromosome constitution has been suggested to be essential for driving tumor progression by enhancing mutagenic mechanisms. The aim of the present study was to determine whether chromosomal changes occur in the su bsequent stages of early laryngeal carcinogenesis and, if so, whether these changes can be of prognostic value. Materials and Methods: Numerical aberrations for chromosomes 1 and 7 were d etected in tissue sections from archival material using an improved in situ hybridization protocol. In total, eight benign laryngeal lesions, 37 prema lignant laryngeal lesions, and 16 specimens containing histologically norma l epithelia adjacent to laryngeal squamous cell carcinomas were studied, Bo th the histologic and the cytogenetic classifications were correlated with progression to laryngeal cancer, Results: No evidence for chromosome alterations was obtained in the control group, nor in histologically normal epithelia adjacent to laryngeal squamo us cell carcinomas, nor in all bur one hyperplastic lesion (n = 11), In con trast, 14 of 15 dysplastic lesions and nine of 11 carcinomas-in-site contai ned numerical chromosomal aberrations, Tetrasomy was present in the majorit y of the dysplastic lesions, An unstable chromosome content (indicated by t he presence of chromosome imbalances and/or polyploidization) in the premal ignant lesion strongly predicted ifs malignant progression. Conclusion: Our results show that laryngeal tumor development involves chro mosome tetraploidization. The further change from a stable to an unstable c hromosome constitution is of importance for malignant progression. J Clin Oncol 18:1644-1651. (C) 2000 by American Society of Clinical Oncolog y.