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




Insulin-like growth factor 1 receptor affects the survival of primary prostate cancer patients depending on TMPRSS2-ERG status - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 17:367

Translational oncology

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.

KeywordsInsulin-like growth factor 1 receptor Prostate cancer TMPRSS2-ERG Prognosis Molecular biotypes AbbreviationsBPFSBiochemical progression-free survival;

CIConfidence interval

cTClinical stage

FFPEFormalin-fixed and paraffin-embedded

FISHFluorescent in situ hybridization

HRHazard ratio

IGFInsulin-like growth factor

IGF-1RIGF-1 receptor

IGFBP-3IGF-binding protein 3

IHCImmunohistochemistry

INSRInsulin receptor

PCaProstate cancer

PFSClinical progression-free survival

pNLymph node pathological stage

PSAProstate specific antigen

pTPathological stage

qRT-PCRQuantitative RT-PCR

RQRelative quantity

SPSpecimen

T2ETMPRSS2-ERG

TMATissue microarray

Electronic supplementary materialThe online version of this article doi:10.1186-s12885-017-3356-8 contains supplementary material, which is available to authorized users.





Author: Caterina Mancarella - Irene Casanova-Salas - Ana Calatrava - Maria García-Flores - Cecilia Garofalo - Andrea Grilli - José

Source: https://link.springer.com/







Related documents