The type 1 insulin-like growth factor receptor is over-expressed in bladder cancer.
OBJECTIVE
To analyse bladder cancer biopsies and investigate the pattern of expression of the type 1 insulin-like growth factor receptor (IGF1R), a receptor tyrosine kinase that mediates tumour cell proliferation, motility and protection from apoptosis.


METHODS
Formalin-fixed specimens of bladder cancer (40 whole-mount, 80 cores on a tumour microarray) and normal bladder (15 samples) were stained immunohistochemically for the IGF1R. The IGF1R expression was also measured by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) on RNA extracted from fresh frozen bladder cancers (61) and benign bladder (12).


RESULTS
Of the 15 samples of normal bladder, 14 showed negligible (1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+) or heavy (4+) staining for IGF1R was detected in 89 (74%) of the 120 samples of malignant urothelium. Q-RT-PCR showed significantly higher levels of steady-state IGF1R mRNA in tumours (all cases, Ta-T4) than in normal bladder (P < 0.05), indicating up-regulation at the transcriptional level. This difference was particularly evident when comparing normal urothelium with superficial (Ta-T1) or invasive (T2-4) tumours; only the latter showed significant IGF1R over-expression at the RNA level (P < 0.05 vs normal bladder).


CONCLUSIONS
The IGF1R is up-regulated in bladder cancer compared with non-malignant bladder, and might contribute to a propensity for invasion.
Rochester
Mark A
MA
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, and Department of Urology, Churchill Hospital, Oxford, UK.
Patel
Nilay
N
Turney
Benjamin W
BW
Davies
David R
DR
Roberts
Ian S
IS
Crew
Jeremy
J
Protheroe
Andrew
A
Macaulay
Valentine M
VM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D011446:Prospective Studies; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D009363:Neoplasm Proteins; D017526:Receptor, IGF Type 1