Abstract
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.
Highlights
Prostate cancer (PCa) is characterized by clinical and biological heterogeneity and has differential outcomes and mortality rates
We analyzed the expression of different components of the insulin-like growth factor (IGF) system and their association with clinico-pathological parameters and the prognosis of biochemical progression-free survival (BPFS) and clinical progression-free survival (PFS) in a retrospective series of 270 patients with primary localized PCa treated with radical prostatectomy
Clinical prostate specimens Formalin-fixed and paraffin-embedded (FFPE) blocks corresponding to radical prostatectomy specimens from 270 PCa patients were retrieved from the archives of the Biobank of the Fundación Instituto Valenciano de Oncología according to the following criteria: specimens obtained from radical retropubic prostatectomies from 1996 to 2002 and no history of previous treatment for PCa, as previously reported [25]
Summary
Prostate cancer (PCa) is characterized by clinical and biological heterogeneity and has differential outcomes and mortality rates. 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. Prostate cancer (PCa) is the most common cancer in men and the sixth cause of cancer death worldwide [1]. Clinical studies evaluating the prognostic potential of IGF-1R are limited and report either positive or negative associations between IGF-1R expression levels and patient outcome [22, 23]. This paper shows for the first time that patients with PCa who do not harbor the T2E rearrangement and who express low levels of IGF-1R represent a subgroup of primary PCa tumors with poor outcome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
