Site-specific molecular signatures predict aggressive disease in hnscc

Thomas J. Belbin, Nicolas F. Schlecht, Richard V. Smith, Leslie R. Adrien, Nicole Kawachi, Margaret Brandwein-Gensler, Aviv Bergman, Quan Chen, Geoffrey J. Childs, Michael B. Prystowsky

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)243-256
Number of pages14
JournalHead and Neck Pathology
Volume2
Issue number4
DOIs
StatePublished - 2008

Fingerprint

Neoplasms
Hypopharynx
Oropharynx
Larynx
Genes
Phenotype
Gene Expression
Gene Expression Profiling
Transcriptome
Mouth
Mucous Membrane
Complementary DNA
Clone Cells
Carcinoma, squamous cell of head and neck
Datasets

Keywords

  • Head and neck cancer
  • Microarray
  • Prognosis
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Otorhinolaryngology

Cite this

Site-specific molecular signatures predict aggressive disease in hnscc. / Belbin, Thomas J.; Schlecht, Nicolas F.; Smith, Richard V.; Adrien, Leslie R.; Kawachi, Nicole; Brandwein-Gensler, Margaret; Bergman, Aviv; Chen, Quan; Childs, Geoffrey J.; Prystowsky, Michael B.

In: Head and Neck Pathology, Vol. 2, No. 4, 2008, p. 243-256.

Research output: Contribution to journalArticle

Belbin TJ, Schlecht NF, Smith RV, Adrien LR, Kawachi N, Brandwein-Gensler M et al. Site-specific molecular signatures predict aggressive disease in hnscc. Head and Neck Pathology. 2008;2(4):243-256. https://doi.org/10.1007/s12105-008-0071-4
Belbin, Thomas J. ; Schlecht, Nicolas F. ; Smith, Richard V. ; Adrien, Leslie R. ; Kawachi, Nicole ; Brandwein-Gensler, Margaret ; Bergman, Aviv ; Chen, Quan ; Childs, Geoffrey J. ; Prystowsky, Michael B. / Site-specific molecular signatures predict aggressive disease in hnscc. In: Head and Neck Pathology. 2008 ; Vol. 2, No. 4. pp. 243-256.
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