Overexpression of IGF1R Predicts Outcome in Invasive Urothelial Carcinoma of Urinary Bladder
Nilda Gonzalez-Roibon, Jenny Kim, Alcides Chaux, Enrico Munari, Sheila F Faraj, Carla Ellis, Rajni Sharma, Trinity Bivalacqua, Mark Schoemberg, Michael Carducci, George J Netto. Johns Hopkins Hospital, Baltimore, MD; Norte University, Asuncion, Paraguay
Background: Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor involved in cell proliferation and differentiation. IGF1R is overexpressed in several tumors including bladder cancer and is currently under investigation as a target of therapy. We explored IGF1R expression in urothelial carcinoma (UC) and its association with clinicopathologic parameters and prognostic role.
Design: Five tissue microarrays (TMA) were constructed from 100 cystectomy specimens performed for invasive UC at our institution (1994 to 2007). Formalin-fixed paraffin-embedded paired tumor and benign samples were spotted 3-4 times each. Membranous IGF1R staining was evaluated using immunohistochemistry (G11, Ventana Medical Systems).A scoring method analogous to that of Her2 expression in breast cancer was used and the highest score was assigned to each tumor. IGF1R was considered overexpressed in cases with score ≥ 1. Endpoints of the study included overall survival (OS) and cancer-specific survival (DSS). Patients were followed-up for a median of 33.5 months (range: 1-141 months).
Results: We found IGF1R overexpression in 62% of UC. No differences were noted between normal urothelium and UC regarding IGF1R overexpression (74% vs. 60%; P=0.14). IGF1R overexpression was more frequent in tumors from African-American patients compared to Caucasians (100% vs. 59%, P=0.04). Tumors at stage pT4 overexpressed IGF1R less frequently than tumors at stages pT1-pT3 (29% vs. 71%, P=0.005). We did not find any association with other analyzed clinicopathologic parameters such as patient's age or gender, muscularis propria invasion, or lymph node metastasis. OS and DSS rates were 58% and 69%, respectively. Patients with tumors overexpressing IGF1R had a lower OS and DSS compared to those without IGF1R overexpression (Mantel-Cox P=0.0007 and P=0.006, respectively). Using Cox proportional hazards regression, IGF1R overexpression remained a significant predictor of OS (HR=3.49, P=0.001) and DSS (HR=3.54, P=0.007) after adjusting for pathologic stage.
Conclusions: Overexpression of IGF1R was found in 62% of UC. High stage tumors overexpressed IGF1R more frequently than low stage tumors. More importantly, IGF1R overexpression was a significant independent predictor of OS and DSS, suggesting its usefulness as a prognisticator in UC.The findings also point to IGF1R as a potential target of therapy in UC.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 197, Tuesday Afternoon