Insulin growth factor receptor-1 expression and loss of PTEN protein predict early recurrence in triple-negative breast cancer
Insulin growth factor receptor-1 expression and loss of PTEN protein predict early recurrence in triple-negative breast cancer
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DOI：
10.1111/j.1365-2559.2012.04255.x
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发表时间：
2012-10-01
期刊：
影响因子：
6.4
通讯作者：
Tan, Puay Hoon
中科院分区：
文献类型：
--
作者：
Iqbal, Jabed;Thike, Aye Aye;Tan, Puay Hoon
目的：胰岛素样生长因子受体-1（IGFR-1）及其信号传导轴促进肿瘤发生、转移和对现有形式的癌症治疗的抗性，并且已经成为抗癌药物开发的主要焦点。由于三阴性乳腺癌（TNBC）的肿瘤学管理选择有限，因此有可能快速开发特异性靶向PTEN-磷酸肌醇3-激酶-AKT途径组分的新型选择性抗癌剂，包括磷酸化形式的AKT（pAKT）和肿瘤抑制分子PTEN。本研究的目的是进行免疫组织化学分析，以检查TNBC中PTEN、IGFR-1和pAKT的表达水平，并确定这些水平是否与该侵袭性乳腺癌子集的不良预后相关。方法和结果：对来自连续队列的144名诊断为TNBC的女性患者的石蜡包埋肿瘤组织进行免疫组织化学。分析IGFR-1、PTEN和pAKT表达与临床病理参数、无病生存期（DFS）和总生存期（OS）的关系。IGFR-1表达（99%）和pAKT表达（92%）显著增加，大多数病例（63%）伴有PTEN表达缺失。IGFR-1表达增加和PTEN表达缺失分别与OS和DFS降低相关。pAKT表达与基底样表达呈强相关。组合免疫表型分析表明，损失的PTEN表达与伴随IGFR-1表达与差DFS.Conclusions：高比例的PTEN损失与IGFR-1和pAKT在TNBC的过度表达表明这些分子的预测早期复发和/或作为目标，在制定有效的替代治疗方案的潜力。
Aims: Insulin-like growth factor receptor-1 (IGFR-1) and its signalling axis promote tumorigenesis, metastasis, and resistance to existing forms of cancer therapy, and have become a major focus for the development of anticancer drugs. As oncological management options for triple-negative breast cancers (TNBCs) are limited, there is potential for the rapid development of novel selective anticancer agents specifically targeting components of the PTEN-phosphoinositide 3-kinase-AKT pathway, including the phosphorylated form of AKT (pAKT) and the tumour suppressor molecule PTEN. The aim of this study was to conduct immunohistochemical analyses to examine the levels of PTEN, IGFR-1 and pAKT expression in TNBCs, and determine whether these levels correlated with poor prognosis in this subset of aggressive breast cancers.Methods and results: Immunohistochemistry was performed on paraffin-embedded tumour tissues from a consecutive cohort of 144 female patients diagnosed with TNBC. Associations of IGFR-1, PTEN and pAKT expression with clinicopathological parameters, disease-free survival (DFS) and overall survival (OS) were evaluated. There were significant increases in IGFR-1 expression (99%) and pAKT expression (92%) with concomitant loss of PTEN expression in the majority of cases (63%). Increased IGFR-1 expression and loss of PTEN expression were associated with reduced OS and DFS, respectively. pAKT expression showed a strong correlation with basal-like expression. Combinatorial immunophenotypic analyses showed that loss of PTEN expression with concomitant IGFR-1 expression correlated with poor DFS.Conclusions: A high percentage of PTEN loss with overexpression of IGFR-1 and pAKT in TNBC indicates the potential of these molecules for predicting early recurrence and/or as targets in the formulation of effective alternative therapy regimens.