title: A prospective, multi-institutional diagnostic trial to determine pathologist accuracy in estimation of percentage of malignant cells.
abstract: BACKGROUND
  The fraction of malignant cells in tumor tissue submitted for tests of genetic alterations is a critical variable in testing accuracy. That fraction is currently determined by pathologist visual estimation of the percentage of malignant cells. Inaccuracy could lead to a false-negative test result.
  
  
  OBJECTIVE
  To describe a prospective, multi-institutional study to determine pathologist estimation accuracy.
  
  
  METHODS
  Ten ×20 magnification images of hematoxylin-eosin-stained colon tissue specimens were sent as an educational component of the College of American Pathologists KRAS-B 2011 Survey. Data from 194 labs were analyzed and compared to a criterion standard with comprehensive manual nuclear counts.
  
  
  RESULTS
  Survey responses indicated low interlaboratory precision of pathologist estimation, but mean estimates were fairly accurate. A total of 5 of the 10 cases assessed showed more than 10% of respondents overestimating in a manner that could lead to false-negative test results.
  
  
  CONCLUSIONS
  The significance of estimation errors resulting in molecular testing failures with implications for patient care is unknown, but the current study suggests false-negative test results may occur.
authors.affiliation: From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut (Dr Viray, Mr Li, Dr Rimm); the Biostatistics (Mr Long) and Surveys (Ms Vasalos) Departments, College of American Pathologists, Northfield, Illinois; the Department of Pathology & Microbiology, University of Nebraska Medical Center, Omaha (Dr Bridge); the Department of Pathology & Laboratory Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Dr Jennings); the Department of Pathology, Mayo Clinic, Rochester, Minnesota (Dr Halling); and the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (Dr Hameed).
authors.forename: Hollis
authors.initials: H
authors.lastname: Viray
authors.forename: Kevin
authors.initials: K
authors.lastname: Li
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Long
authors.forename: Patricia
authors.initials: P
authors.lastname: Vasalos
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bridge
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Jennings
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Halling
authors.forename: Meera
authors.initials: M
authors.lastname: Hameed
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002452:Cell Count; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D003625:Data Collection; D011905:Genes, ras; D006801:Humans; D007753:Laboratories; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D015588:Observer Variation; D010338:Pathology, Clinical; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012955:Societies, Medical; D014481:United States; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins