Does Mitosis Specific Marker PHH3 Help Grading Upper Tract Urothelial Carcinomas in Cell Blocks?
Charalambos Solomides, Ruth Birbe, Demetrius Bagley, Marluce Bibbo. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Grading upper tract urothelial carcinomas in cell blocks can be challenging. The interobserver agreement is poor among pathologists. Mitotic figure (MF) counting along with nuclear features is important in grading these tumors, however, artifacts, presence of apoptosis and rarity of MFs in a given lesion can hamper the task. We evaluated the use of the mitotic specific marker phospho-histone H3 (PHH3) as an adjunct to H&E stain for grading upper tract urothelial carcinomas in cell blocks.
Design: Formalin fixed paraffin embedded tissue from cell blocks of 61 urothelial carcinomas were stained with H&E and PHH3-antibody. Grading of tumors was performed by three pathologists in a blind fashion, first on H&E and then on both H&E and PHH3 stained slides. The grading system used was the 1973 WHO three point grading system. Gradings were compared across pathologists and for H&E staining versus PHH3 plus H&E staining with the Stuart-Maxwell test of marginal homogeneity that accounts for the matched data. The percent agreement and the kappa statistic were used to assess agreement. Statistical analyses were conducted in SAS 9.2 (SAS Institute Inc., Cary, NC) and Stata 11.2 (StataCorp, College Station, TX).
Results: Table 1 summarizes the inter-rater agreement between the three study pathologists.
|Percent Agreement (95% CI)|
|I/II||56% (43%, 68%)||84% (74%, 93%)||0.002|
|II/III||48% (35%, 60%)||75% (65%, 86%)||0.003|
|I/III||61% (48%, 73%)||82% (72%, 92%)||0.016|
|kAPPA (95% CI)|
|I/II||0.32 (0.16, 049)||0.74 (0.56, 0.92)|
|II/III||0.21 (0.05, 0.37)||0.61 (0.42, 0.79)|
|I/III||0.36 (0.18, 0.55)||0.71 (0.53, 0.89)|