Chromosome Instabi l i t y as an Indicator of Mal ignant Progress ion in Laryngeal Mucosa

predict whether premalignant laryngeal lesions will progress toward invasive growth. The acquisition of changes in chromosome constitution has been sug-gested 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 subsequent stages of early laryn-geal carcinogenesis and, if so, whether these changes can be of prognostic value. Materials and Methods: Numerical aberrations for chromosomes 1 and 7 were detected in tissue sections from archival material using an improved in situ hybrid-ization protocol. In total, eight benign laryngeal lesions, 37 premalignant laryngeal lesions, and 16 specimens containing histologically normal epithelia adjacent to la-ryngeal squamous cell carcinomas were studied. Both the histologic and the cytogenetic classifications were corre-lated 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 squamous cell carcinomas, nor in all but one hyperplastic lesion (n 5 11). In contrast, 14 of 15 dysplastic lesions and nine of 11 carcinomas-in-situ contained numerical chromo-somal aberrations. Tetrasomy was present in the majority of the dysplastic lesions. An unstable chromo-some content (indicated by the presence of chromo-some imbalances and/or polyploidization) in the pre-malignant lesion strongly predicted its malignant progression. Conclusion: Our results show that laryngeal tumor development involves chromosome tetraploidization. The further change from a stable to an unstable chro-mosome constitution is of importance for malignant progression