title: Does mitosis-specific marker phosphohistone H3 help the grading of upper tract urothelial carcinomas in cell blocks?
abstract: BACKGROUND
  Grading upper tract urothelial carcinomas (UTUC) in cell blocks with small distorted tissue fragments can be challenging; interobserver agreement is poor among pathologists. Mitotic figure (MF) counting along with nuclear features is important in grading these tumors. We evaluated the use of the mitotic-specific marker phosphohistone H3 (PHH3) as an adjunct to hematoxylin and eosin (H&E) stain for grading UTUC in cell blocks.
  
  
  METHODS
  Formalin-fixed, paraffin-embedded tissues from the cell blocks of 61 UTUC were stained with H&E and PHH3 antibody. The grading of tumors was performed independently by 3 pathologists, on both H&E-stained and PHH3 plus H&E-stained slides. The grading system used was the 1973 WHO 3-point grading system. Gradings were compared by all the pathologists for H&E staining versus PHH3 plus H&E staining with the Stuart-Maxwell test of marginal homogeneity that accounts for the matched data.
  
  
  RESULTS
  The average pairwise agreement by H&E alone was 55%, and 80% by PHH3 plus H&E.
  
  
  CONCLUSIONS
  By adding PHH3 immunostain to the H&E, the agreement in grading the carcinomas among the 3 pathologists improved dramatically. PHH3 immunostain may play an important role in grading UTUC in small cell block samples.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA. charalambos.solomides@jefferson.edu
authors.forename: Charalambos C
authors.initials: CC
authors.lastname: Solomides
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Birbe
authors.forename: Nicos
authors.initials: N
authors.lastname: Nicolaou
authors.forename: Demetrius
authors.initials: D
authors.lastname: Bagley
authors.forename: Marluce
authors.initials: M
authors.lastname: Bibbo
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008940:Mitotic Index / Q000379:methods*; D060787:Neoplasm Grading / Q000379:methods*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D010750:Phosphoproteins