Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer.
Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer.
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DOI：
10.1186/1471-2407-11-31
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发表时间：
2011-01-25
期刊：
影响因子：
3.8
通讯作者：
Aglietta M
中科院分区：
文献类型：
--
作者：
Peraldo-Neia C;Migliardi G;Mello-Grand M;Montemurro F;Segir R;Pignochino Y;Cavalloni G;Torchio B;Mosso L;Chiorino G;Aglietta M
表皮生长因子受体（EGFR）的激活突变赋予对酪氨酸激酶抑制剂（TKi）、吉非替尼和厄洛替尼的敏感性。我们分析了前列腺癌（PC）的EGFR表达，EGFR突变状态和基因表达谱，为EGFR靶向治疗提供理论依据。对100例PC患者的根治性乳腺癌切除术后肿瘤组织进行EGFR TK结构域（外显子18 - 21）突变分析和EGFR免疫组化。使用寡核苷酸微阵列的基因表达谱也进行了51个PC样品。在36%的肿瘤样本中发现EGFR蛋白过表达（EGFR高），在13%的样本中发现突变。与表达低水平EGFR（EGFR低）的肿瘤患者相比，EGFR高肿瘤患者的生化复发风险显著增加（风险比-HR 2.52，p=0.02）。微阵列分析没有发现EGFR高和EGFR低肿瘤之间的基因表达有任何差异。相反，在EGFR高肿瘤中，我们能够识别出79个基因签名，将突变的肿瘤与非突变的肿瘤区分开来。此外，发现29个基因在突变/EGFR高（n=3）和突变/EGFR低肿瘤（n=5）之间差异表达。其中4个下调基因U19/EAF 2、ABCC 4、KLK 3和ANXA 3以及1个上调基因FOXC 1参与PC进展。根据我们的研究结果，我们假设EGFR状态的准确定义可以改善预后分层，我们建议EGFR导向治疗在PC患者中可能发挥作用。我们的结果是在相对较小的患者样本中产生的，因此需要在更大的系列中进行确认。
Activating mutations of the epidermal growth factor receptor (EGFR) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease. Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples. EGFR protein overexpression (EGFRhigh) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFRhigh tumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFRlow). Microarray analysis did not reveal any differences in gene expression between EGFRhigh and EGFRlow tumours. Conversely, in EGFRhigh tumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFRhigh (n=3) and mutated/EGFRlow tumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression. Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.
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影响因子：
158.5
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Lynch, TJ;Bell, DW;Haber, DA
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Haber, DA
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