title: Validation of ovarian cancer gene expression signatures for survival and subtype in formalin fixed paraffin embedded tissues.
abstract: BACKGROUND
  Gene expression signatures have been identified for epithelial ovarian cancer survival (TCGA) and intrinsic subtypes (Tothill et al.). One obstacle to clinical translation is that these signatures were developed using frozen tissue, whereas usually only formalin-fixed, paraffin embedded (FFPE) tissue is available. The aim of this study was to determine if gene expression signatures can be translated to fixed archival tissues.
  
  
  METHODS
  RNA extracted from FFPE sections from 240 primary ovarian cancers was analyzed by DASL on Illumina BeadChip arrays. Concordance of expression at the individual gene level was assessed by comparing array data from the same cancers (30 frozen samples analyzed on Affymetrix arrays versus FFPE DASL).
  
  
  RESULTS
  The correlation between FFPE and frozen survival signature estimates was 0.774. The TCGA signature using DASL was predictive of survival in 106 advanced stage high grade serous ovarian cancers (median survival 33 versus 60 months, estimated hazard ratio for death 2.30, P=0.0007). Similar to Tothill, we found using DASL that most high grade serous ovarian cancers (102/110, 93%) were assigned to subtypes 1, 2, 4 and 5, whereas most endometrioid, clear cell, mucinous and low grade serous cases (39/57, 68%) were assigned to subtypes 3 and 6 (P<10e-15).
  
  
  CONCLUSIONS
  Although individual probe estimates of microarrays may be weakly correlated between FFPE and frozen samples, combinations of probes have robust ability to predict survival and subtype. This suggests that it may be possible to use these signatures for prognostic and predictive purposes as we seek to individualize the treatment of ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Sfakianos
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Iversen
authors.forename: Regina
authors.initials: R
authors.lastname: Whitaker
authors.forename: Liudmila
authors.initials: L
authors.lastname: Akushevich
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Marks
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
mesh_terms: D005260:Female; D005557:Formaldehyde; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016612:Paraffin Embedding
chemical_list: D005557:Formaldehyde