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To investigate the prognostic significance of chromosomal aberrations of chromosomes X and 11 in relation to disease-specific survival in head and neck squamous cell carcinoma.University hospital.A 10-year retrospective clinical study. Information about clinical findings, treatment, and follow-up has been recorded prospectively.By means of the fluorescence in situ hybridization technique with centromeric probes for chromosomes X and 11, we analyzed 40 randomly selected patients before treatment for T1 to T4 head and neck squamous cell carcinoma. Numerical aberrations were scored and evaluated in frozen sections.The significance of prognostic parameters was tested by the log-rank and Kaplan-Meier methods for the univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis.Numerical aberrations of chromosome 11 correlated positively with T and N classification (P = .03 and P = .02, respectively) and with clinical stage (P = .02). Patients with higher frequencies of numerical aberrations for both chromosome X (>48%, mean) and chromosome 11 (>57%, mean) had shortened disease-specific survival compared with those with lower frequencies of numerical aberrations (P = .008 and P<.001, respectively). Of patients who died from disease within 3 years, 7 (50%) had a trisomic value of chromosome 11 of 35% or higher of nuclei (P<.001). Moreover, patients with a higher value (≥8%) of amplification of chromosome 11 (>4 signals) were associated with having poor prognosis compared with those with a lower value (P = .02).Numerical aberrations of chromosomes X and 11 had prognostic value in head and neck squamous cell carcinoma, and higher frequencies of numerical aberrations correlated with poor prognosis.