Rochester Mark A, Patel Nilay, Turney Benjamin W, Davies David R, Roberts Ian S, Crew Jeremy, Protheroe Andrew, Macaulay Valentine M
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, and Department of Urology, Churchill Hospital, Oxford, UK.
BJU Int. 2007 Dec;100(6):1396-401. doi: 10.1111/j.1464-410X.2007.06931.x. Epub 2007 Jul 23.
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.
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).
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).
The IGF1R is up-regulated in bladder cancer compared with non-malignant bladder, and might contribute to a propensity for invasion.
分析膀胱癌活检样本,研究1型胰岛素样生长因子受体(IGF1R)的表达模式。IGF1R是一种受体酪氨酸激酶,可介导肿瘤细胞增殖、运动及抗凋亡作用。
对福尔马林固定的膀胱癌标本(40个全层标本,80个肿瘤组织芯片上的组织芯)和正常膀胱标本(15个样本)进行IGF1R免疫组化染色。还通过定量逆转录-聚合酶链反应(Q-RT-PCR)检测新鲜冰冻膀胱癌组织(61例)和良性膀胱组织(12例)中IGF1R的表达。
15例正常膀胱样本中,14例显示IGF1R免疫染色可忽略不计(1+)或弱阳性(2+)。相比之下,120例恶性尿路上皮样本中有89例(74%)检测到IGF1R中度(3+)或强阳性(4+)染色。Q-RT-PCR显示,肿瘤(所有病例,Ta-T4)中稳态IGF1R mRNA水平显著高于正常膀胱(P<0.05),表明在转录水平上调。当比较正常尿路上皮与浅表性(Ta-T1)或浸润性(T2-4)肿瘤时,这种差异尤为明显;只有后者在RNA水平显示出显著的IGF1R过表达(与正常膀胱相比,P<0.05)。
与非恶性膀胱相比,膀胱癌中IGF1R上调,可能促使肿瘤具有侵袭性。