Novel Biomarkers Expression in Patients with Superficial and Minimally Invasive Urothelial Bladder Cancer and Their Assoaciation with Tumor Outcomes
L Ali, FR Herrmann, RT Cheney, P Mhawech-Fauceglia. Roswell Park Cancer Institiute, Buffalo, NY; University of Geneva, Geneva, Switzerland
Background: Numerous novel genes have been identified in urothelial bladder cancer (UBC) and genes including ninjurin, synuclein and neuropilin seemed to be associated with invasive tumors and aggressive behavior. This study is the first to evaluate the protein expression of these biomarkers and to reveal their prognostic value in large series of superficial (pTa) and minimally invasive (pT1) UBC cases with a long and adequate follow-up. The aims of the our study was: 1- to evaluate the expressions of each of synuclein, ninjurin and neuropilin protein in superficial and minimally invasive tumors, 2- to define their value in predicting tumor outcomes such as recurrence and progression.
Design: Tissue microarray was done on 183 paraffin-embedded tumor tissues (pTa 81, pT1 102). Immunohistochemistry for synuclein, ninjurin and neuropilin was performed on paraffin blocks. Statistical analysis was performed to define the association between each of these biomarkers, clinical data and tumor outcomes.
Results: A statistically significant association was observed between synuclein expression and tumor stage (p=0.029). In univariate Cox model among these 3 biomarkers only ninjurin was associated with tumor progression (ninjurin weak vs negative: HR 0.21, 95% CI [0.07-0.62] to ninjurin strong vs negative: HR 0.17 95% CI [0.06-0.50]; p= 0.001). Multivariate analysis revealed that only tumor grade was independent predictor of pTa/pT1 tumor recurrence and progression. Likewise, high-grade (G3) tumors are more often to progress than those well differentiated tumors with HR 23.57 (95% CI 5.64-98.53 p<0.001). In addition, high-grade tumors are more often to recur than those of low-grade tumors with HR 2.61 (95% CI 1.23-5.52, p 0.012).
Conclusions: We found that tumors with strong synuclein expressions are likely to be more advanced tumors (pT1). In addition, tumors expressing ninjurin tend to progress slower than those with no ninjurin expressions. Finally, synuclein and neuropilin failed to show any value in predicting tumor behavior. Still the best independent factor in predicting pTa/pT1 tumor recurrence and progression is tumor grade.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 109, Monday Morning