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Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC

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Abstract

It is known that head and neck squamous cell carcinomas (HNSCC) originating from different anatomic locations can exhibit varying behavior that is not predictable by histopathology of the primary tumor. Using a microarray containing 27,323 cDNA clones, we generated sets of gene expression profiles for 36 HNSCC primary tumors (12 oral cavity, 12 oropharynx, and 12 larynx/hypopharynx). From these datasets, we ranked genes according to their ability to differentiate between patients whose disease progressed within a 24 month period (aggressive phenotype) and those that did not (non-aggressive phenotype) based on levels of gene expression. A merging of datasets from the three sites revealed that only a fraction of identified genes were shared between any two sites. This contrasted greatly with the significant overlap (approximately 50%) in down-regulated genes identified in tumor/normal comparisons using cases both from oropharynx and larynx/hypopharynx. From these data, we conclude that HNSCC tumors originating from different anatomic sites share consistent changes in gene expression when comparing primary tumors to normal adjacent mucosa; these common changes most likely reflect alterations required for tumor development. In contrast, once a tumor has developed, tumor-host interactions at the different anatomic sites are likely responsible for the site-specific signatures associated with aggressive versus non-aggressive disease. Predictions of outcome based on gene expression profiling are therefore heavily influenced by the anatomic site of the primary tumor.

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Acknowledgments

The authors would like to thank Aldo Massimi and the Albert Einstein College of Medicine Microarray Facility for their assistance. This study was supported by a grant from the US National Cancer Institute, CA104402 (to TJB).

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Authors and Affiliations

  1. Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Thomas J. Belbin, Leslie R. Adrien, Nicole Kawachi, Margaret Brandwein-Gensler, Quan Chen, Geoffrey Childs & Michael B. Prystowsky

  2. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Nicolas F. Schlecht

  3. Department of Otorhinolaryngology – Head and Neck Surgery, Montefiore Medical Center, Medical Arts Pavilion, 3400 Bainbridge Avenue, Bronx, NY, 10467, USA

    Richard V. Smith

  4. Department of Systems and Computational Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Aviv Bergman

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  1. Thomas J. Belbin
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  2. Nicolas F. Schlecht
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  3. Richard V. Smith
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  4. Leslie R. Adrien
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Correspondence to Thomas J. Belbin.

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Belbin, T.J., Schlecht, N.F., Smith, R.V. et al. Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC. Head and Neck Pathol 2, 243–256 (2008). https://doi.org/10.1007/s12105-008-0071-4

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  • DOI: https://doi.org/10.1007/s12105-008-0071-4

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