[436] 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.

Inter-Rater Agreement Among Pathologists Using H&E or PHH3+H&E Staining

	H&E	PHH3+H&E	P*
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)

I=First Pathologist; II=Second Pathologist; III=Third Pathologist. (*) P-value compares the percent agreement by H&E alone to that by PHH3+H&E


Conclusions: By adding PHH3 immunostain to the H&E, the agreement in grading the carcinomas among the three pathologists improved dramatically (Table 1, average pairwise agreement = 80%, overall kappa = 0.69). PHH3 immunostain may play an important role in grading upper tract urothelial carcinomas in small cell block samples.
Category: Cytopathology

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 71, Tuesday Morning