Insulin-like growth factor-1 receptor expression in upper tract urothelial carcinoma

Marie Lisa Eich, Aline C. Tregnago, Sheila F. Faraj, Doreen N. Palsgrove, Kazutoshi Fujita, Stephania M. Bezerra, Enrico Munari, Rajni Sharma, Alcides Chaux, George J. Netto

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1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalVirchows Archiv
Volume474
Issue number1
DOIs
StatePublished - Jan 18 2019
Externally publishedYes

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Keywords

  • IGF1R
  • Insulin-like growth factor-1 receptor
  • Upper tract urothelial carcinoma
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Eich, M. L., Tregnago, A. C., Faraj, S. F., Palsgrove, D. N., Fujita, K., Bezerra, S. M., Munari, E., Sharma, R., Chaux, A., & Netto, G. J. (2019). Insulin-like growth factor-1 receptor expression in upper tract urothelial carcinoma. Virchows Archiv, 474(1), 21-27. https://doi.org/10.1007/s00428-018-2468-0