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与中枢神经系统转移发展相关的三阴性乳腺癌表型的特征描述。

Characterisation of the triple negative breast cancer phenotype associated with the development of central nervous system metastases.

作者信息

Laimito Katerin Rojas, Gámez-Pozo Angelo, Sepúlveda Juan, Manso Luis, López-Vacas Rocío, Pascual Tomás, Fresno Vara Juan A, Ciruelos Eva

机构信息

Department of Medical Oncology, Hospital 12 de Octubre, Av. de Córdoba, s/n, 28041, Spain.

I+D Department, Biomedica Molecular Medicine, CLAID building, Campus de Cantoblanco, Calle Faraday, 7, Madrid 28049, Spain.

出版信息

Ecancermedicalscience. 2016 Apr 11;10:632. doi: 10.3332/ecancer.2016.632. eCollection 2016.

Abstract

AIMS

Breast cancer (BC) is the most frequent tumour in women, representing 20-30% of all malignancies, and continues to be the leading cause of cancer deaths among European women. Triple-negative (TN) BC biological aggressiveness is associated with a higher dissemination rate, with central nervous system (CNS) metastases common. This study aims to elucidate the association between gene expression profiles of PTGS2, HBEGF and ST6GALNAC5 and the development of CNS metastases in TNBC.

METHODS

This is a case-controlled retrospective study comparing patients (pts) with CNS metastases versus patients without them after adjuvant treatment. The selection of the samples was performed including 30 samples in both case and control groups. Formalin-fixed, paraffin-embedded samples were retrieved from the Hospital 12 de Octubre Biobank. Five 10 µm sections from each FFPE sample were deparaffinised with xylene and washed with ethanol, and the RNA was then extracted with the RecoverAll Kit (Ambion). Gene expression was assessed using TaqMan assays.

RESULTS

A total of 53 patients were included in the study. The average age was 55 years (range 25-85). About 47 patients (88.67%) had ductal histology and presented high grade (III) tumours (40 patients; 75.47%). Eight women in the case group presented first distant recurrence in the CNS (34.80%), local recurrence (three patients, 13.04%), lungs (two patients; 8.7%), bone (one patient; 4.34%) and other locations (seven patients; 30.38%). In the control group, first distant recurrence occurred locally (six patients; 46.1%), in bone (two patients; 15.4%), lungs (one patient; 7.7%) and other sites (four patients; 23.1%). RNA was successfully obtained from 53 out of 60 samples. PTGS2, HBEGF, and ST6GALNAC5 expression values were not related to metastasis location.

CONCLUSION

TN tumours frequently metastasise to the visceral organs, particularly lungs and brain, and are less common in bone. The literature suggests that expression of the three genes of interest (PTGS2, HBEGF, and ST6GALNAC5) could be different in TNBC patients with CNS metastasis when compared to patients without it. We did not find a differential expression pattern in PTGS2, HBEGF, and ST6GALNAC5 genes in primary TNBC showing CNS metastases. Further studies are needed to clarify the role of these genes in CNS metastases in TNBC patients.

摘要

目的

乳腺癌(BC)是女性中最常见的肿瘤,占所有恶性肿瘤的20%-30%,并且仍然是欧洲女性癌症死亡的主要原因。三阴性(TN)乳腺癌的生物学侵袭性与较高的播散率相关,中枢神经系统(CNS)转移很常见。本研究旨在阐明PTGS2、HBEGF和ST6GALNAC5的基因表达谱与TNBC中CNS转移发生之间的关联。

方法

这是一项病例对照回顾性研究,比较辅助治疗后发生CNS转移的患者与未发生CNS转移的患者。样本选择时病例组和对照组均纳入30个样本。从10月12日医院生物样本库中检索福尔马林固定、石蜡包埋的样本。每个FFPE样本切取5张10μm切片,用二甲苯脱蜡,乙醇洗涤,然后用RecoverAll试剂盒(Ambion)提取RNA。使用TaqMan检测法评估基因表达。

结果

本研究共纳入53例患者。平均年龄为55岁(范围25-85岁)。约47例患者(88.67%)为导管组织学类型,表现为高级别(III级)肿瘤(40例患者;75.47%)。病例组中有8名女性首次远处复发发生在CNS(34.80%)、局部复发(3例患者,13.04%)、肺部(2例患者;8.7%)、骨骼(1例患者;4.34%)和其他部位(7例患者;30.38%)。对照组中,首次远处复发发生在局部(6例患者;46.1%)、骨骼(2例患者;15.4%)、肺部(1例患者;7.7%)和其他部位(4例患者;23.1%)。60个样本中有53个成功获得RNA。PTGS2、HBEGF和ST6GALNAC5的表达值与转移部位无关。

结论

TN肿瘤常转移至内脏器官,尤其是肺和脑,在骨骼中较少见。文献表明,与未发生CNS转移的TNBC患者相比,发生CNS转移的TNBC患者中这三种感兴趣基因(PTGS2、HBEGF和ST6GALNAC5)的表达可能不同。我们在出现CNS转移的原发性TNBC中未发现PTGS2、HBEGF和ST6GALNAC5基因的差异表达模式。需要进一步研究以阐明这些基因在TNBC患者CNS转移中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/043c/4854224/97dd93051938/can-10-632fig1.jpg

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