Association of ErbB1-4 expression in invasive breast cancer with clinicopathological characteristics and prognosis
Association of ErbB1-4 expression in invasive breast cancer with clinicopathological characteristics and prognosis
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DOI：
10.1007/s12282-012-0415-5
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发表时间：
2014-07-01
期刊：
影响因子：
4
通讯作者：
Iwase, Hirotaka
中科院分区：
文献类型：
--
作者：
Fujiwara, Saori;Ibusuki, Mutsuko;Iwase, Hirotaka
人表皮生长因子受体2型(Her2)/ErbB2在浸润性乳腺癌的发生和发展中起关键作用。然而，其他ErbB家族成员与乳腺癌患者预后的相关性长期以来一直存在争议。在250例原发性浸润性乳腺癌患者中，我们采用实时定量PCR技术对ErbB1-4 mRNA表达水平和基因拷贝数进行了全面分析。评价ErbB1-4水平与临床病理特征及预后的关系。ErbB2基因的mRNA表达量与拷贝数呈显著相关（P = 0.0005），而其他ErbB基因的mRNA表达量与拷贝数无显著相关（P = 0.0005）。ErbB3和ErbB4 mRNA表达量呈正相关（P < 0.0001）。ErbB1/2 mRNA表达与雌激素受体（ER）和孕激素受体（PgR）阳性呈负相关，ErbB3/4 mRNA表达与雌激素受体（ER）和孕激素受体（PgR）阳性呈正相关。Kaplan-Meier生存分析显示ErbB1 mRNA表达与生存率降低相关。ErbB2和ErbB3 mRNA表达与生存均无关联，因为一半her2阳性肿瘤患者接受曲妥珠单抗治疗。ErbB4 mRNA的高表达对乳腺癌特异性存活预后良好，erbb3、ErbB4 mRNA的表达以及ErbB1、ErbB2 mRNA的表达可能是组织病理因素。ErbB3 mRNA在er阳性肿瘤中高表达，其预后价值存在争议。ErbB4 mRNA表达与ER阳性及预后良好相关，提示ErbB4可能参与ER依赖性生长。
Human epidermal growth factor receptor type 2 (Her2)/ErbB2 plays a key role in the initiation and progression of invasive breast cancer. However, the prognostic relevance to breast cancer patients of the other ErbB family members has long been a matter of debate.In a series of 250 primary invasive breast cancer patients, we performed a comprehensive analysis of ErbB1-4 at the levels of mRNA expression and gene copy number using real-time quantitative PCR. The relationship between the status of ErbB1-4 and the clinicopathological characteristics or prognosis was evaluated.The mRNA expression of ErbB2, but not the other ErbB genes, was significantly correlated to copy number (P = 0.0005). ErbB3 and ErbB4 mRNA expression were positively correlated to each other (P < 0.0001). The mRNA expression of ErbB1/2 was inversely correlated to estrogen receptor (ER) and progesterone receptor (PgR) positivity, although mRNA expression of ErbB3/4 was positively correlated to ER and PgR positivity. Kaplan-Meier survival analysis showed that ErbB1 mRNA expression was associated with reduced survival. Neither ErbB2 nor ErbB3 mRNA expression had any association with survival, because half of the patients with Her2-positive tumors were treated with trastuzumab. High ErbB4 mRNA expression showed good prognosis with respect to breast cancer-specific survivalErbB3 and ErbB4 mRNA expression, as well as well as that of ErbB1 and ErbB2, could be histopathological factors. ErbB3 mRNA was highly expressed in ER-positive tumors and has controversial prognostic value. ErbB4 mRNA expression was well correlated with ER positivity and good prognosis, indicating that ErbB4 may contribute to ER-dependent growth.