title: Evaluation of mitotic activity index in breast cancer using whole slide digital images.
abstract: BACKGROUND
  Mitotic Activity Index (MAI) is an important independent prognostic factor and an integral part of the breast cancer grading system. Thus, correct estimation of this prognostically relevant feature is essential for guiding treatment decision and assessing patient prognosis. The aim of this study was to validate the use of high resolution Whole Slide Images (WSI) in estimating MAI in breast cancer specimens.
  
  
  METHODS
  MAI was evaluated in 100 consecutive breast cancer specimens by three observers on two occasions, microscopically and on WSI with a wash out period of 4 months. MAI was also translated to mitotic scores as in grading. Inter- and intra-observer agreement between microscopic and digital MAI counts and scores was measured.
  
  
  RESULTS
  Almost perfect inter-observer agreements were obtained from counting MAI using a conventional microscope (intra-class correlation coefficient (ICCC) 0.879) as well as on WSI (ICCC 0.924). K coefficients reflected good inter-observer agreements among observers' microscopic mitotic scores (average kappa 0.642). Comparable results were also observed among digital mitotic scores (average kappa 0.635). There was strong to perfect intra-observer agreements between MAI counts and mitotic scores for the two diagnostic modalities (ICCC 0.716-0.863, kappa 0.506-0.617). There were no significant differences in mitotic scores using both diagnostic modalities.
  
  
  CONCLUSIONS
  Scoring mitoses using WSI in breast cancer seems to be just as reliable and reproducible as when using a microscope. Further development of software and image quality will definitely encourage the use of WSI in routine pathology practice.
authors.affiliation: Symbiant Pathology Expert Centre, Alkmaar, The Netherlands.
authors.forename: Shaimaa
authors.initials: S
authors.lastname: Al-Janabi
authors.affiliation: Symbiant Pathology Expert Centre, Alkmaar, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: van Slooten
authors.affiliation: Symbiant Pathology Expert Centre, Zaandam, The Netherlands.
authors.forename: Mike
authors.initials: M
authors.lastname: Visser
authors.affiliation: Medical Center Alkmaar, Alkmaar, The Netherlands.
authors.forename: Tjeerd
authors.initials: T
authors.lastname: van der Ploeg
authors.affiliation: Department of pathology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: Symbiant Pathology Expert Centre, Alkmaar, The Netherlands.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Jiwa
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008938:Mitosis; D060787:Neoplasm Grading; D010336:Pathology / Q000379:methods