IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer.
View/ Open
Date
2017-11-21ICR Author
Author
Aleksic, T
Verrill, C
Bryant, RJ
Han, C
Worrall, AR
Brureau, L
Larré, S
Higgins, GS
Fazal, F
Sabbagh, A
Haider, S
Buffa, FM
Cole, D
Macaulay, VM
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Activated type 1 insulin-like growth factor receptors (IGF-1Rs) undergo internalisation and nuclear translocation, promoting cell survival. We previously reported that IGF-1R inhibition delays DNA damage repair, sensitising prostate cancer cells to ionising radiation. Here we tested the clinical relevance of these findings. METHODS: We assessed associations between IGF-1R and clinical outcomes by immunohistochemistry in diagnostic biopsies of 136 men treated with 55-70 Gy external beam radiotherapy for prostate cancer, comparing results with publicly available transcriptional data in surgically treated patients. RESULTS: Following radiotherapy, overall recurrence-free survival was shorter in patients whose tumours contained high total, cytoplasmic and internalised (nuclear/cytoplasmic) IGF-1R. High total IGF-1R associated with high primary Gleason grade and risk of metastasis, and cytoplasmic and internalised IGF-1R with biochemical recurrence, which includes patients experiencing local recurrence within the radiation field indicating radioresistance. In multivariate analysis, cytoplasmic, internalised and total IGF-1R were independently associated with risk of overall recurrence, and cytoplasmic IGF-1R was an independent predictor of biochemical recurrence post radiotherapy. Insulin-like growth factor receptors expression did not associate with biochemical recurrence after radical prostatectomy. CONCLUSIONS: These data reveal increased risk of post-radiotherapy recurrence in men whose prostate cancers contain high levels of total or cytoplasmic IGF-1R.
Collections
Subject
Humans
Prostatic Neoplasms
Neoplasm Recurrence, Local
Receptor, IGF Type 1
Neoplasm Staging
Aged
Middle Aged
Male
Language
eng
Date accepted
2017-08-30
Citation
British journal of cancer, 2017, 117 (11), pp. 1600 - 1606
Publisher
NATURE PUBLISHING GROUP