NE-AUA 2006 Annual Meeting, September 28 - 30, 2006, The Westin Hotel & Rhode Island Convention Center Providence, Rhode Island
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The RNA-binding Protein IMP3: A Novel Molecular Marker Predicts Progression of Superficial (Ta and T1) Urothelial Carcinomas of Bladder
Lioudmila Sitnikova, MD, Gary Mendese, Zhong Jiang, MD.
Umass Medical Center, Worcester, MA,

Background: Majority of urothelial carcinomas (UC) are superficial tumors including noninvasive tumors (Ta and Tis, carcinoma in situ, CIS) and the tumors with lamina propria invasion (T1). Superficial UCs are a heterogeneous disease with a viable natural history. Clinically, it is crucial to identify a subgroup of the superficial UCs with aggregative progression. In this study, we investigated whether IMP3, an oncofetal RNA-binding protein, can serve as a biomarker to predict progression of superficial UCs.
Methods: A total of 208 patients with superficial UCs (Ta, N=180; T1, N=28; Tis, N=14; Grade I, N=83; Grade II, N=80; Grade III, N=31 and CIS, N=14) at the University of Massachusetts Medical Center were studied for progression free survival. The tumor progression was defined as further invasion or metastasis later proved by pathology diagnosis, and no progression was defined as negative report from the follow-up bladder biopsy or from follow-up combined urine cytology and cystoscopy. The expression of IMP3 in UC tissues was evaluated by immunohistochemistry.
Results: The expression of IMP3 was significantly increased not only in the high grade Ta UCs and T1 tumors but most importantly also in a subset of Ta and T1 tumor that were much more likely to have subsequently progression.Kaplan-Meier plots and log-rank tests showed that patients without IMP3 expression in their Ta and T1 UCs had significant longer progression-free survival than patients with IMP3 expression (P=0.013). In patients whose superficial UCs were negative for IMP3, the 5-year progression-free survival rates were 87% (Ta) and 70% (T1) respectively, whereas in patients with IMP3 positive superficial UCs, the progression free survival rates were 56% (Ta) and 13% (T1) respectively. Multivariate Cox proportional hazards regression analysis showed that the hazard ratio of IMP3 status in superficial UCs were 3.13 (progression-free survival, P=0.001), which were much higher than the hazard ratios associated with tumor grades.
Conclusions: IMP3 is an excellent independent prognostic marker that can be used to identify a group of patients with superficial UC that have a higher potential for progression. In noninvasive Ta UCs, presence of IMP3 can be used as a marker to identify a subgroup of patients with lesions that behave like T1 cancers. These findings may thus have implications of modifying patientsí follow-up plans and/or therapeutic strategies.


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