A Comparison of Proliferation Markers in Urothelial Carcinomas of the Urinary Bladder.
Ok M Mangrud, Bianca D Hidle, Rune Waalen, Einar Gudlaugsson, Emiel AM Janssen, Jan PA Baak. Stavanger University Hospital, Norway; University of Bergen, Norway; Innlandet Hospital Trust, Lillehammer, Norway
Background: In Norway, 1218 new urinary bladder cancer patients were diagnosed in 2008. Treatment depends heavily on grade and TaT1 stage, but observer prognostic variability in staging and grading is considerable which may have strong implications for patients. A URO-QP model consisting of the following features: proliferation associated biomarker Ki67, mitotic activity index (MAI), and the mean area of the 10 largest nuclei (MNA10) has been developed. Lately we have added Phosphohistone H3, a marker of cells in late G2 and M phase.
Design: Patients with primary urothelial carcinoma of the urinary bladder diagnosed at a university hospital 2002-2006 with long follow up were included into the study. All specimens were routinely graded according to the WHO 73 system and analyzed according to the URO-QP model. Grading according to the WHO 2004 system was performed after archival specimen retrieval. ROC analysis was used to calculate cut-off values for MNA10, MAI and PPH3. Kaplan-Meier curves and Cox regression analysis were used to analyse the prognostic value of the variables with recurrence or stage progression as end-points.
Results: 194 patients were included. Mean follow-up was 53.4 months (range 1-101). Nineteen of the patients (10 %) progressed to a higher stage; 6.8 % of the patients with grade 1 tumours, 4.1% of the patients with grade 2 tumours and 23.1 % of the patients with grade 3 tumours (p=0.001), or 4.2 % of the patients with low grade tumours and 18.7 % of the patients with high grade tumours (p=0.001).
In agreement with previous studies, ROC curve analysis showed the following thresholds: MNA10>136.4, Ki67>18 and MAI>4. PPH3 threshold was >23. Patients with MNA10>136.4 showed 24% stage progression, contrasting 5% of those with lower MNA10. (p<0.001). This was the strongest identifier of patients with progression (p<0.001, Hazard Ratio=6.2, 95% confidence interval 2.3 – 16.8). None of the morphological grading systems, Ki67, PPH3, or MAI had additional prognostic value.
Conclusions: None of the variables analyzed showed any significant prognostic value for recurrence. For stage progression all proliferation markers, MNA10, and grading had independent prognostic value. In multivariate analysis MNA10 with a threshold of 136.4 um was the only remaining factor overshadowing all the other factors.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 183, Tuesday Morning