乳腺癌中生长因子浓度的增加和 EGFR 系统的激活。

Increased concentrations of growth factors and activation of the EGFR system in breast cancer.

机构信息

Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark.

出版信息

Clin Chem Lab Med. 2012 Oct 1;50(10):1809-18. doi: 10.1515/cclm-2011-0823.

DOI:10.1515/cclm-2011-0823

PMID:23089711

Abstract

BACKGROUND

In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values.

METHODS

Samples of malignant and non-cancer autologous reference tissue were collected from 415 breast cancer patients. The tissue samples were cut and either paraffin-embedded or homogenized in a lysis buffer to extract the proteins. HER2 was measured using both immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and ADVIA Centaur. Phosphorylated HER2 and EGFR (pHER2, pEGFR), total EGFR and the ligands: epidermal growth factor (EGF), transforming growth factor-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin (BTC) and epiregulin (EREG) were measured using the Luminex.

RESULTS

The HER2 positivity rate was determined to be 25.2% by the Centaur method vs. 15.8% by IHC and FISH. HER2, HB-EGF, TGFα and AREG were upregulated in cancer tissue as compared with autologous reference tissue while EGFR, pEGFR and EGF were downregulated (p<10-6). pEGFR in autologous reference tissue was negatively correlated to the number of positive lymph nodes and to the tumor size (p=0.0007 and p=0.001, respectively) and furthermore, decreased in the group of mastectomy operated patients as compared with the lumpectomy group (p<10-6). HB-EGF in cancer tissue was positively associated with high grade tumors (p<10-6) and pHER2, HB-EGF and BTC were associated with poor disease free survival (p=0.017, p=0.012 and p=0.0026, respectively).

CONCLUSIONS

Our study demonstrated a profound activation of the EGFR system. HB-EGF was increased by factor 10 in cancer tissue and related to the biological aggressiveness of the tumors, and pHER2, HB-EGF and BTC were associated with poor clinical outcome.

摘要

背景

本研究同时测定了乳腺癌患者组织样本中表皮生长因子受体 1（EGFR）和 2（HER2）的总蛋白和磷酸化蛋白含量，以及 EGFR 配体，以探讨它们之间的相互关系和可能的预后价值。

方法

从 415 例乳腺癌患者中采集恶性和非癌自体参考组织样本。将组织样本切开，或石蜡包埋，或在裂解缓冲液中匀浆以提取蛋白。使用免疫组化（IHC）/荧光原位杂交（FISH）和 ADVIA Centaur 同时检测 HER2。使用 Luminex 测定磷酸化 HER2 和 EGFR（pHER2、pEGFR）、总 EGFR 以及配体：表皮生长因子（EGF）、转化生长因子-α（TGFα）、双调蛋白（AREG）、肝素结合表皮生长因子样生长因子（HB-EGF）、β-细胞素（BTC）和表皮调节素（EREG）。

结果

Centaur 法检测的 HER2 阳性率为 25.2%，而 IHC 和 FISH 法检测的阳性率为 15.8%。与自体参考组织相比，癌组织中 HER2、HB-EGF、TGFα 和 AREG 上调，而 EGFR、pEGFR 和 EGF 下调（p<10-6）。自体参考组织中的 pEGFR 与阳性淋巴结数量和肿瘤大小呈负相关（p=0.0007 和 p=0.001），并且在接受乳房切除术的患者组中与接受保乳术的患者组相比降低（p<10-6）。癌组织中的 HB-EGF 与高级别肿瘤呈正相关（p<10-6），pHER2、HB-EGF 和 BTC 与无病生存不良相关（p=0.017、p=0.012 和 p=0.0026）。