title: Site-specific molecular signatures predict aggressive disease in HNSCC.
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.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. tbelbin@aecom.yu.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Belbin
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.forename: Richard V
authors.initials: RV
authors.lastname: Smith
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Adrien
authors.forename: Nicole
authors.initials: N
authors.lastname: Kawachi
authors.forename: Margaret
authors.initials: M
authors.lastname: Brandwein-Gensler
authors.forename: Aviv
authors.initials: A
authors.lastname: Bergman
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Childs
authors.forename: Michael B
authors.initials: MB
authors.lastname: Prystowsky
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D003131:Combined Modality Therapy; D018450:Disease Progression; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009062:Mouth Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010610:Pharyngeal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate