Reproducibility of Grading Papillary Urothelial Carcinoma of Bladder. Utility of RB, P53 and KI-67.
Yulan Gong, J Steve Hou, Xiaoli Chen, Robert T Ownbey, Bethany L Mapow, Fernando U Garcia. Drexel University College of Medicine, Philadelphia, PA
Background: Two histopathological features stratify Bladder Cancer treatment in its initial phase. Histological grade: Low (LG) and high (HG) and the status of lamina propria invasion. Interobserver variability in grading papillary urothelial carcinoma (PUC) is well documented (Miyamoto, 2010). The aim was to assess the reproducibility of grading PUC and to assess the utility of a panel expression (P53, RB and Ki-67).
Design: 92 consecutive cases (TURB and biopsies), with primary PUC of the bladder diagnosed from 1/2001 to 6/2010 were retrieved from the University Hospital. 20 additional cases were not included due to different diagnosis and slides not being available. Five pathologists graded de-identified H&E slides using WHO/ISUP 2004 criteria for the first review (R1). On the second review (R2) (interval 3-4 weeks), image analysis % expression for panel was provided. A weighted Kappa (κ) coefficient was generated against the original pathology diagnosis (R1 and R2) and between pathologists using PASS software. Unpaired t-test was used to analyze panel expression.
Results: 59 men (64.1%) and 33 women (35.9%) with age range 39 to 93 years (mean 68±13) constituted the study group. 50 LG (39 non-invasive (NI) and 11 invasive (IN)) and 42 HG (7 NI and 35 IN) were reviewed. Consensus is reached in 67.4% and 64.1% on R1 and R2. Reproducibility with original diagnosis is high for R1 (κ ranging 0.678 to 0.770, mean 0.745±0.039) and R2 (κ ranging 0.682 to 0.758, mean 0.718±0.041). The intra-observer reproducibility for each pathologist is 0.827, 0.855, 0.734, 0.854 and 0.674. Agreement amongst pathologists is high in the R1 (κ ranging 0.741 to 0.841, mean 0.796±0.036) & R2 (κ ranging 0.764 to 0.829, mean 0.786±0.030). HG-IN has the highest agreement in R1 and R2 (80%, 85.7%), followed by LG-NI (71.8%, 61.5%). HG-NI and LG-IN have the lowest agreement in R1 and R2 (14.3%, 28.6% & 45.5%, 27.3%). The panel increased agreement with original diagnosis in the HG-NI by 14.3% and HG-IN by 5.7%. Expression of each panel marker was studied for HG and LG groups. In HG, RB expression is decreased (52.8±33.0% to 35.6±38.9%, p<0.05), P53 expression is increased (21.8±28.4% to 43.4±37.7%, p<0.05) and Ki-67 expression is increased (29.1±23.0% to 61.1±25.7%, p<0.05).
Conclusions: 1) WHO/ISUP 2004 classification of PUC grading is highly reproducible in a non-specialized academic department. 2) Panel expression information did not increase grading reproducibility overall but did improve it in HG group. 3) Loss of RB and increased P53 and Ki-67 expression correlates with HG tumor.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 184, Tuesday Morning