Fujiwara Saori, Ibusuki Mutsuko, Yamamoto Satoko, Yamamoto Yutaka, Iwase Hirotaka
Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Breast Cancer. 2014 Jul;21(4):472-81. doi: 10.1007/s12282-012-0415-5. Epub 2012 Oct 26.
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 survival
ErbB3 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.
人表皮生长因子受体2（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的预后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，我们使用实时定量PCR对ErbB1-4在mRNA表达水平和基因拷贝数水平进行了综合分析。评估了ErbB1-4状态与临床病理特征或预后之间的关系。
ErbB2的mRNA表达而非其他ErbB基因的表达与拷贝数显著相关（P = 0.0005）。ErbB3和ErbB4的mRNA表达呈正相关（P < 0.0001）。ErbB1/2的mRNA表达与雌激素受体（ER）和孕激素受体（PgR）阳性呈负相关，而ErbB3/4的mRNA表达与ER和PgR阳性呈正相关。Kaplan-Meier生存分析表明，ErbB1的mRNA表达与生存率降低相关。由于一半的Her2阳性肿瘤患者接受了曲妥珠单抗治疗，因此ErbB2和ErbB3的mRNA表达与生存率均无关联。高ErbB4 mRNA表达在乳腺癌特异性生存方面显示出良好的预后。
ErbB3和ErbB4的mRNA表达以及ErbB1和ErbB2的表达可能是组织病理学因素。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阳性和良好预后密切相关，表明ErbB4可能有助于ER依赖性生长。
