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Identification of Novel Prognosticators of Outcome in Squamous Cell Carcinoma of the Head and Neck

From the Laboratory of Epithelial Cancer Biology, Head and Neck Service, Departments of Surgery, Epidemiology and Biostatistics, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and Department of Pediatrics, Baylor College of Medicine, Houston, TX

Address reprint requests to Bhuvanesh Singh, MD, Laboratory of Epithelial Cancer Biology, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: singhb{at}mskcc.org

PURPOSE: The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC).

PATIENTS AND METHODS: We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate ² statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than .15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the ² approximation of the final model by MCS.

RESULTS: CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P = .0009 to P = .01).

CONCLUSION: HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.

Supported in part by the Young Investigator Award from the American Society of Clinical Oncology and the George H.A. Clowes, Jr, MD, FACS, Memorial Research Career Development Award from the American College of Surgeons.

V.B.W. and W.S. contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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