title: Gene expression profiles of lung adenocarcinoma linked to histopathological grading and survival but not to EGF-R status: a microarray study.
abstract: BACKGROUND
  Several different gene expression signatures have been proposed to predict response to therapy and clinical outcome in lung adenocarcinoma. Herein, we investigate if elements of published gene sets can be reproduced in a small dataset, and how gene expression profiles based on limited sample size relate to clinical parameters including histopathological grade and EGFR protein expression.
  
  
  METHODS
  Affymetrix Human Genome U133A platform was used to obtain gene expression profiles of 28 pathologically and clinically annotated adenocarcinomas of the lung. EGFR status was determined by fluorescent in situ hybridization and immunohistochemistry.
  
  
  RESULTS
  Using unsupervised clustering algorithms, the predominant gene expression signatures correlated with the histopathological grade but not with EGFR protein expression as detected by immunohistochemistry. In a supervised analysis, the signature of high grade tumors but not of EGFR overexpressing cases showed significant enrichment of gene sets reflecting MAPK activation and other potential signaling cascades downstream of EGFR. Out of four different previously published gene sets that had been linked to prognosis, three showed enrichment in the gene expression signature associated with favorable prognosis.
  
  
  CONCLUSIONS
  In this dataset, histopathological tumor grades but not EGFR status were associated with dominant gene expression signatures and gene set enrichment reflecting oncogenic pathway activation, suggesting that high immunohistochemistry EGFR scores may not necessarily be linked to downstream effects that cause major changes in gene expression patterns. Published gene sets showed association with patient survival; however, the small sample size of this study limited the options for a comprehensive validation of previously reported prognostic gene expression signatures.
authors.affiliation: Institute of Pathology, University Hospital Freiburg, Breisacher Str 115a, 79106 Freiburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.forename: Friedrich
authors.initials: F
authors.lastname: Feuerhake
authors.forename: Gian
authors.initials: G
authors.lastname: Kayser
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.forename: Konrad
authors.initials: K
authors.lastname: Aumann
authors.forename: Bernward
authors.initials: B
authors.lastname: Passlick
authors.forename: Paul
authors.initials: P
authors.lastname: Fisch
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Axel
authors.initials: A
authors.lastname: Zur Hausen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
chemical_list: D066246:ErbB Receptors