Tran T N, Selinger C I, Yu B, Ng C C, Kohonen-Corish M R J, McCaughan B, Kennedy C, O'Toole S A, Cooper W A
Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
J Clin Pathol. 2014 Nov;67(11):985-91. doi: 10.1136/jclinpath-2014-202347. Epub 2014 Aug 12.
Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane receptor involved in tumourigenesis that may be a potential therapeutic target. We aimed to investigate the incidence and prognostic significance of alterations in IGF1R copy number, and IGF1R protein expression in resected primary non-small cell lung cancer (NSCLC), and lymph node metastases.
IGF1R gene copy number status was evaluated by chromogenic silver in situ hybridisation and IGF1R protein expression was evaluated by immunohistochemistry in tissue microarray sections from a retrospective cohort of 309 surgically resected NSCLCs and results were compared with clinicopathological features, including EGFR and KRAS mutational status and patient survival.
IGF1R gene copy number status was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1% exhibited IGF1R gene amplification. High IGF1R expression was found in 28.3%. There was a modest correlation between IGF1R gene copy number and protein expression (r=0.2, p<0.05). Alterations of IGF1R gene copy number and protein expression in primary tumours were significantly associated with alterations in lymph node metastases (p<0.01). High IGF1R gene copy number and protein expression was significantly higher in squamous cell carcinomas (SCC) compared with other subtypes of NSCLC (p<0.05). There were no other associations between IGF1R status and other clinicopathological features including patient age, gender, smoking status, tumour size, stage, grade, EGFR or KRAS mutational status or overall survival.
High IGF1R gene copy number and protein overexpression are frequent in NSCLC, particularly in SCCs, but they are not prognostically relevant.
胰岛素样生长因子-1受体（IGF1R）是一种参与肿瘤发生的酪氨酸激酶膜受体，可能是一个潜在的治疗靶点。我们旨在研究IGF1R拷贝数改变以及IGF1R蛋白表达在切除的原发性非小细胞肺癌（NSCLC）及淋巴结转移中的发生率和预后意义。
通过显色银原位杂交评估IGF1R基因拷贝数状态，采用免疫组织化学法在组织芯片切片上评估IGF1R蛋白表达，该组织芯片来自309例手术切除的NSCLC回顾性队列，将结果与临床病理特征进行比较，包括表皮生长因子受体（EGFR）和KRAS突变状态以及患者生存率。
29.2%的NSCLC中IGF1R基因拷贝数状态为阳性（高多体性或扩增），12.1%表现出IGF1R基因扩增。28.3%发现IGF1R高表达。IGF1R基因拷贝数与蛋白表达之间存在适度相关性（r = 0.2，p < 0.05）。原发性肿瘤中IGF1R基因拷贝数和蛋白表达的改变与淋巴结转移的改变显著相关（p < 0.01）。与NSCLC的其他亚型相比，鳞状细胞癌（SCC）中IGF1R基因拷贝数和蛋白高表达显著更高（p < 0.05）。IGF1R状态与其他临床病理特征之间无其他关联，包括患者年龄、性别、吸烟状态、肿瘤大小、分期、分级、EGFR或KRAS突变状态或总生存期。
NSCLC中IGF1R基因高拷贝数和蛋白过表达很常见，尤其是在SCC中，但它们与预后无关。
