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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues
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uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues

机译：血液和组织中单个乳腺癌细胞中的uPAR和HER-2基因状态

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摘要

overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively.
机译：乳腺癌中尿激酶纤溶酶原激活物系统或HER-2（erbB-2）的过表达与预后不良有关。 HER-2过表达是由HER-2基因扩增引起的。抗HER-2抗体曲妥珠单抗可显着改善HER2阳性乳腺癌的临床结局。针对uPA系统的药物正在早期临床试验中。这项研究的目的是确定是否发生尿激酶纤溶酶原激活物受体（uPAR）基因扩增，以及对血液或组织中单个肿瘤细胞（TCs）的分析是否可以为常规病理分析增加信息，从而有助于诊断和治疗。对单个TC的分析表明，uPAR扩增发生在大部分原发性乳腺癌以及晚期疾病患者的循环肿瘤细胞（CTC）中。触摸准备（TPs）与原发肿瘤中HER-2和uPAR基因状态的常规病理检查之间完全一致。如果考虑到CTC中HER-2基因扩增的获得，那么原发性肿瘤与CTC之间的HER-2基因状态也具有极好的一致性。出乎意料的是，在同一TC和患者中，HER-2和uPAR的基因扩增最频繁，这表明生物学偏倚和共扩增的潜在优势。 HER-2和uPAR在原发性肿瘤中的表达分别预测了100％和92％的患者的基因状态。

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