Overexpression of IGF1R predicts outcome in invasive urothelial carcinoma of urinary bladder
Year: 2016
Type: other
Abstract: 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 carcinoma 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 (60% vs. 74%; 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. 69%, 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. CONCLUSION: Overexpression of IGF1R was found in 62% of UC. More importantly, IGF1R overexpression was a significant independent predictor of OS and DSS, suggesting its usefulness as a prognosticator in UC. The findings also point to IGF1R as a potential target of therapy in UC.
Institution: Universidad del Norte
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2734347943