title: Can we accurately report PTEN status in advanced colorectal cancer?
abstract: BACKGROUND
  Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results.
  
  
  METHODS
  We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed.
  
  
  RESULTS
  Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%).
  
  
  CONCLUSIONS
  Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hocking
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Hardingham
authors.forename: Vy
authors.initials: V
authors.lastname: Broadbridge
authors.forename: Joe
authors.initials: J
authors.lastname: Wrin
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Townsend
authors.forename: Niall
authors.initials: N
authors.lastname: Tebbutt
authors.forename: John
authors.initials: J
authors.lastname: Cooper
authors.forename: Andrew
authors.initials: A
authors.lastname: Ruszkiewicz
authors.forename: Chee
authors.initials: C
authors.lastname: Lee
authors.affiliation: The Queen Elizabeth Hospital, TQEH Woodville Road, Woodville South, SA 5011, Australia. timothy.price@health.sa.gov.au.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Price
mesh_terms: D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015588:Observer Variation; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics*; D017384:Sequence Deletion; D016037:Single-Blind Method
chemical_list: D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human