ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis
ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis
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DOI：
10.1093/annonc/mdm431
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发表时间：
2008-01-01
影响因子：
50.5
通讯作者：
Peyrat, J. -P.
中科院分区：
文献类型：
--
作者：
Revillion, F.;Lhotellier, V.;Peyrat, J. -P.
背景：本研究的目的是提供ErbB/HER配体在乳腺癌中的表达谱。分析其与受体的关系、生物病理学特征及预后。表皮生长因子（EGF）、转化生长因子-α（TGF α），双调蛋白（AREG），β细胞素（BTC），肝素结合EGF样生长因子（HB-EGF），采用TaqMan探针，通过实时逆转录-聚合酶链反应，对363例肿瘤中的表皮调节蛋白（EREG）和神经调节蛋白-1-4（NRG 1 -4）进行定量。配体的检出率为80%~ 96%，NRG 3和EREG的检出率分别为42%和45.5%。在304例病例中至少表达一种配体（截止值：上四分位数）。几乎观察到受体和配体共表达的所有组合，但TGF α在共表达EGFR/HER 3、NRG 3的肿瘤中优先表达，在共表达EGFR/HER 4的肿瘤中优先表达，在共表达HER 2/HER 4的肿瘤中优先表达AREG和EREG。EGF和AREG与雌二醇受体、小肿瘤大小、低组织预后分级、高HER 4水平相关。TGF α、HB-EGF和NRG 2与这些参数呈负相关。在考克斯单因素分析中，EGF是一个预后因子。结论：我们的研究表明，（i）ErbB/HER配体，包括BTC和EREG，在大多数乳腺癌中表达;（ii）TGF α，HB-EGF和NRG 2高表达与肿瘤的生物学侵袭性有关。
Background: The aim of this study is to provide an expression profile of ErbB/HER ligands in breast cancer. We analysed the relationships with their receptors, the bio-pathological features and prognosis.Patients and methods: Epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), amphiregulin (AREG), betacellulin (BTC), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EREG) and neuregulins-1-4 (NRG1-4) were quantified in 363 tumours by real-time reverse transcription-polymerase chain reaction using TaqMan probes.Results: Ligands were detected in 80%-96% of the cases, except NRG3 (42%) and EREG (45.5%). At least one ligand was expressed in 304 cases (cut-off: upper quartile). Almost all combinations of receptor and ligand co-expressions were observed, but TGF alpha is preferentially expressed in tumours co-expressing EGFR/HER3, NRG3 in those co-expressing EGFR/HER4, AREG and EREG in those co-expressing HER2/HER4. EGF and AREG were associated with estradiol receptors, small tumour size, low histoprognostic grading, high HER4 levels. TGF alpha, HB-EGF and NRG2 were negatively related to these parameters. In Cox univariate analyses, EGF was a prognostic factor.Conclusion: Our study demonstrates that (i) ErbB/HER ligands, including BTC and EREG, are expressed in most breast cancers; and (ii) TGF alpha, HB-EGF and NRG2 high expressions are related to the biological aggressiveness of the tumours.