title: A methodology for utilization of predictive genomic signatures in FFPE samples.
abstract: BACKGROUND
  Gene expression signatures developed to measure the activity of oncogenic signaling pathways have been used to dissect the heterogeneity of tumor samples and to predict sensitivity to various cancer drugs that target components of the relevant pathways, thus potentially identifying therapeutic options for subgroups of patients. To facilitate broad use, including in a clinical setting, the ability to generate data from formalin-fixed, paraffin-embedded (FFPE) tissues is essential.
  
  
  METHODS
  Patterns of pathway activity in matched fresh-frozen and FFPE xenograft tumor samples were generated using the MessageAmp Premier methodology in combination with assays using Affymetrix arrays. Results generated were compared with those obtained from fresh-frozen samples using a standard Affymetrix assay. In addition, gene expression data from patient matched fresh-frozen and FFPE melanomas were also utilized to evaluate the consistency of predictions of oncogenic signaling pathway status.
  
  
  RESULTS
  Significant correlation was observed between pathway activity predictions from paired fresh-frozen and FFPE xenograft tumor samples. In addition, significant concordance of pathway activity predictions was also observed between patient matched fresh-frozen and FFPE melanomas.
  
  
  CONCLUSIONS
  Reliable and consistent predictions of oncogenic pathway activities can be obtained from FFPE tumor tissue samples. The ability to reliably utilize FFPE patient tumor tissue samples for genomic analyses will lead to a better understanding of the biology of disease progression and, in the clinical setting, will provide tools to guide the choice of therapeutics to those most likely to be effective in treating a patient's disease.
authors: Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC 27708, USA.
authors: Jennifer A
authors: JA
authors: Freedman
authors: Christina K
authors: CK
authors: Augustine
authors: Angelica M
authors: AM
authors: Selim
authors: Kirsten C
authors: KC
authors: Holshausen
authors: Zhengzheng
authors: Z
authors: Wei
authors: Katherine A
authors: KA
authors: Tsamis
authors: David S
authors: DS
authors: Hsu
authors: Holly K
authors: HK
authors: Dressman
authors: William T
authors: WT
authors: Barry
authors: Douglas S
authors: DS
authors: Tyler
authors: Joseph R
authors: JR
authors: Nevins
mesh_terms: D000818:Animals; D005260:Female; D005404:Fixatives / Q000737:chemistry; D005557:Formaldehyde / Q000737:chemistry; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D008545:Melanoma / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016612:Paraffin Embedding; D016707:Tissue Fixation / Q000379:methods
chemical_list: D005404:Fixatives; D005557:Formaldehyde