Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor that plays a crucial role in cell proliferation, growth, differentiation, and apoptosis. IGF1R overexpression has been observed in several cancers, including invasive bladder carcinomas, as a potential prognostic factor. Given known biologic differences between upper and lower urinary tract urothelial carcinoma, we assessed the expression status and prognostic significance of IGF1R in upper tract urothelial carcinoma (UTUC). Two tissue microarrays (TMAs) were built from 99 Japanese patients with non-metastatic UTUC submitted to radical nephroureterectomy between 1997 and 2011. TMAs were constructed with triplicate tumor and paired benign urothelium. Membranous IGF1R staining was evaluated using immunohistochemistry. Two scoring methods were applied (Her2-score and H-score). The highest score was assigned to each tumor. IGF1R positivity was defined as Her2-score ≥ 1+. Association with clinicopathologic parameters and outcome was assessed using hazard ratios (HR) with 95% confidence intervals (CI) and adjusted P values. We found positive IGF1R expression in 70% of UTUC. Outcomes were as follows: tumor recurrence, 33%; tumor progression, 59%; overall mortality, 33%; and cancer-specific mortality, 30%. IGF1R was not associated with any clinicopathologic features. In addition, IGF1R expression was not associated with tumor recurrence (HR = 0.54, CI = 0.25–1.1, P = 0.11), tumor progression (HR = 1.6, CI = 0.8–3.1, P = 0.19), overall mortality (HR = 1.5, CI = 0.68–3.4, P = 0.31), or cancer-specific mortality (HR = 1.6, CI = 0.68–3.8, P = 0.27). Positive IGF1R expression was found in more than two thirds of UTUC. This finding provides a rationale to investigate IGF1R as a potential therapeutic target in UTUC. In contrast to bladder cancer, IGF1R expression in UTUC did not correlate with outcome, further pointing to biologic differences between UTUC and bladder cancer.
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GJN conceived and designed the study and wrote, edited, and reviewed the manuscript. MLE analyzed and interpreted data and wrote, edited, and reviewed the manuscript. AC analyzed data and wrote, edited, and reviewed the manuscript. DNP edited and reviewed the manuscript. KF collected samples and clinical data on cohort and reviewed and edited the manuscript. RS performed immunohistochemical analysis and reviewed the manuscript. ACT, SFF, SMB, and EM collected and analyzed data and reviewed the manuscript.
All authors gave final approval for publication. GJN takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Written informed consent was obtained from all the patients included in the study.
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