Combined and Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading.

The and genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of and gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the and genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The and amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined and amplification allowed us to distinguish three cancer risk subgroups, and and co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of and amplification in early laryngeal tumorigenesis. Remarkably, amplification was found to be an independent cancer predictor. Furthermore, combined and amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.