胺氧化酶在乳腺癌转移灶中的位点特异性表达。

Site-specific expression of amine oxidases in breast cancer metastases.

作者信息

Cha Yoon Jin, Jung Woo Hee, Koo Ja Seung

机构信息

Department of Pathology, College of Medicine and Severance Hospital, Yonsei University, Seoul, South Korea.

出版信息

Tumour Biol. 2018 May;40(5):1010428318776822. doi: 10.1177/1010428318776822.

DOI:10.1177/1010428318776822

PMID:29775160

Abstract

We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0.001), tumoral diamine oxidase ( p = 0.003), stromal diamine oxidase ( p = 0.047), and stromal monoamine oxidase B ( p = 0.002) were differentially expressed in different metastatic sites. Bone metastases showed low expression of lysyl oxidase, tumoral diamine oxidase, and stromal diamine oxidase. We observed high expression of lysyl oxidase in brain metastases, tumoral diamine oxidase in liver metastases, stromal diamine oxidase in lung metastases, and stromal monoamine oxidase B in bone metastases. Lysyl oxidase positivity was associated with progesterone receptor negativity ( p = 0.001), and monoamine oxidase A positivity was associated with human epidermal growth factor receptor-2 negativity ( p = 0.003) and the luminal A subtype ( p = 0.003). On univariate analysis shorter overall survival was associated with stromal diamine oxidase negativity ( p = 0.008), especially in lung metastases ( p = 0.025), and stromal monoamine oxidase B positivity ( p < 0.001). Stromal monoamine oxidase B positivity was an independent prognostic factor for shorter overall survival in multivariate Cox analysis (hazard ratio, 4.069; 95% confidence interval, 1.649-10.04; p = 0.002). Finally, in metastatic breast cancer, amine oxidase-related proteins were differentially expressed in a manner specific to metastatic site, and stromal monoamine oxidase B expression was correlated with prognosis.

摘要

我们旨在评估胺氧化酶相关蛋白在转移性乳腺癌组织中的表达，并确定其临床意义。共从126例转移性乳腺肿瘤构建组织芯片（31例骨转移（24.6%），36例脑转移（28.6%），11例肝转移（8.7%），48例肺转移（38.1%））。对胺氧化酶相关蛋白（赖氨酰氧化酶、二胺氧化酶、单胺氧化酶A和B）进行免疫组化染色。在转移性乳腺癌组织中，赖氨酰氧化酶（p = 0.001）、肿瘤二胺氧化酶（p = 0.003）、间质二胺氧化酶（p = 0.047）和间质单胺氧化酶B（p = 0.002）在不同转移部位存在差异表达。骨转移显示赖氨酰氧化酶、肿瘤二胺氧化酶和间质二胺氧化酶低表达。我们观察到脑转移中赖氨酰氧化酶高表达，肝转移中肿瘤二胺氧化酶高表达，肺转移中间质二胺氧化酶高表达，骨转移中间质单胺氧化酶B高表达。赖氨酰氧化酶阳性与孕激素受体阴性相关（p = 0.001），单胺氧化酶A阳性与人类表皮生长因子受体-2阴性相关（p = 0.003）及管腔A型亚型相关（p = 0.003）。单因素分析显示，总体生存期较短与间质二胺氧化酶阴性相关（p = 0.008），尤其是在肺转移中（p = 0.025），以及与间质单胺氧化酶B阳性相关（p < 0.001）。在多因素Cox分析中，间质单胺氧化酶B阳性是总体生存期较短的独立预后因素（风险比，4.069；95%置信区间，1.649 - 10.04；p = 0.002）。最后，在转移性乳腺癌中，胺氧化酶相关蛋白在转移部位特异性表达存在差异，且间质单胺氧化酶B表达与预后相关。