Genetic imbalances with impact on survival in head and neck cancer patients

Abstract

Chromosomal imbalances in 113 primary head and neck squamous cell carcinomas (HNSCCs) determined by comparative genomic hybridization were correlated with patients survival using custom-made computer software which enabled the assessment of individual chromosomal loci. The Kaplan-Meier analysis revealed that overrepresentations of 2q12, 3q21-29, 6p21.1, 11q13, 14q23, 14q24, 14q31, 14q32, 15q24, 16q22, and deletions of 8p21-22 and 18q11.2 were significantly associated with both shorter disease-free interval and disease-specific survival in this tumor collective. Multivariate Cox proportional hazards regression models consistently identified the gains of 3q21-29, 11q13, and the loss of 8p21-22 as independent prognostic markers carrying a higher significance than the nodal status as the only clinicopathological parameter with statistical importance. In addition, these three markers allowed a molecular dissection of the patients with low clinical risk (pN0 and pT2 tumors). Thus, the genomic data being derived from the evaluation of primary HNSCC enabled a stratification of the patients into subgroups with different survival highlighting the necessity of a genetically based tumor classification for refining diagnosis and treatment of HNSCC patients.

Figure 1.

A–C: Kaplan-Meier plots comparing disease-specific survival in patients whose tumors showed gains at 3q21-29 (A), gains at 11q13 (B), deletions at 8p21-22 (C) represented by solid lines with that of patients whose tumors did not exhibit the specific chromosomal imbalances (stippled lines), respectively. D: Kaplan-Meier plot comparing disease-specific survival in patients whose tumors had already spread to cervical lymph nodes with that of patients whose tumors did not metastasize at time of diagnosis (stippled line).

Figure 2.

Summary of chromosomal alterations in 113 HNSCC in a histogram representation. The chromosomal imbalances are shown as incidence curves along each chromosome. Areas on the left side of the chromosome ideogram correspond to loss of genetic material; those on the right side to DNA gains. The frequency of alterations can be determined from 0.5 (50%) and 1.0 (100%) incidence lines depicted parallel to the chromosome ideograms. DNA changes with 99% significance are colored in gray, additional changes with 95% significance are depicted in light gray. The proportion of pronounced DNA gains and losses being defined as imbalances for which the ratio profiles exceeded the thresholds of 1.5 and 0.5, respectively, are visualized in black.