Insulin-like growth factor 1 receptor affects the survival of primary prostate cancer patients depending on TMPRSS2-ERG status

BMC Cancer

Research Article

Andrea Grilli¹  Caterina Mancarella¹  Cecilia Garofalo¹  Katia Scotlandi¹  Ana Calatrava²  José Rubio-Briones³  Maria García-Flores⁴  José Antonio López-Guerrero⁴  Irene Casanova-Salas⁴ 

[1] CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, Rizzoli Orthopedic Institute, via di Barbiano, 1/10, 40136, Bologna, Italy;Department of Pathology, Fundación Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena, 8, 46009, Valencia, Spain;Department of Urology, Fundación Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena, 8, 46009, Valencia, Spain;Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena, 8, 46009, Valencia, Spain;

关键词: Insulin-like growth factor 1 receptor;    Prostate cancer;    TMPRSS2-ERG;    Prognosis;    Molecular biotypes;   

DOI  :  10.1186/s12885-017-3356-8

 received in 2016-09-01, accepted in 2017-05-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundProstate cancer (PCa) is characterized by clinical and biological heterogeneity and has differential outcomes and mortality rates. Therefore, it is necessary to identify molecular alterations to define new therapeutic strategies based on the risk of progression. In this study, the prognostic relevance of the insulin-like growth factor (IGF) system was examined in molecular subtypes defined by TMPRSS2-ERG (T2E) gene fusion within a series of patients with primary localized PCa.MethodsA cohort of 270 formalin-fixed and paraffin-embedded (FFPE) primary PCa samples from patients with more than 5 years’ follow-up was collected. IGF-1R, IGF-1, IGFBP-3 and INSR expression was analyzed using quantitative RT-PCR. The T2E status and immunohistochemical ERG findings were considered in the analyses. The association with both biochemical and clinical progression-free survival (BPFS and PFS, respectively) was evaluated for the different molecular subtypes using the Kaplan-Meier proportional risk log-rank test and the Cox proportional hazards model.ResultsAn association between IGF-1R overexpression and better BPFS was found in T2E-negative patients (35.3% BPFS, p-value = 0.016). Multivariate analysis demonstrated that IGF-1R expression constitutes an independent variable in T2E-negative patients [HR: 0.41. CI 95% (0.2–0.82), p = 0.013]. These data were confirmed using immunohistochemistry of ERG as subrogate of T2E. High IGF-1 expression correlated with prolonged BPFS and PFS independent of the T2E status.ConclusionsIGF-1R, a reported target of T2E, constitutes an independent factor for good prognosis in T2E-negative PCa. Quantitative evaluation of IGF-1/IGF-1R expression combined with molecular assessment of T2E status or ERG protein expression represents a useful marker for tumor progression in localized PCa.

【 授权许可】

CC BY   
© The Author(s). 2017