Williams Virginie, Grosset Andrée-Anne, Zamorano Cuervo Natalia, St-Pierre Yves, Sylvestre Marie-Pierre, Gaboury Louis, Grandvaux Nathalie
CRCHUM - Centre de recherche du Centre Hospitalier de l'Université de Montréal, 900 rue Saint-Denis, Montréal, Qc H2X 0A9, Canada.
Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Qc, Montréal, Canada.
BMC Cancer. 2017 May 22;17(1):356. doi: 10.1186/s12885-017-3321-6.
IKKε is an oncogenic kinase that was found amplified and overexpressed in a substantial percentage of human breast cancer cell lines and primary tumors using genomic and gene expression analyses. Molecular studies have provided the rational for a key implication of IKKε in breast cancer cells proliferation and invasiveness through the phosphorylation of several substrates.
Here, we performed immunohistochemical detection of IKKε expression on tissue microarrays constituted of 154 characterized human breast cancer tumors. We further determined the association with multiple clinicopathological parameters and 5-years overall, disease-free and distant disease free survival.
We observed expression of IKKε in 60.4% of the breast cancer tumors. IKKε expression status showed no association with a panel of markers used for molecular classification of the tumors, including ER/PR/HER2 status, or with the molecular subtypes. However, IKKε expression was inversely associated with lymph node metastasis status (p = 0.0032). Additionally, we identified a novel association between IKKε and EGFR expression (p = 0.0011).
The unexpected observation of an inverse association between IKKε and lymph node metastasis advocates for larger scale immunohistochemical profiling of primary breast tumors to clarify the role of IKKε in metastasis. This study suggests that breast cancer tumors expressing EGFR and IKKε may be potential targets for drugs aiming at inhibiting IKKε activity or expression.
IKKε是一种致癌激酶,通过基因组和基因表达分析发现,在相当比例的人类乳腺癌细胞系和原发性肿瘤中存在扩增和过表达。分子研究为IKKε通过磷酸化多种底物在乳腺癌细胞增殖和侵袭中发挥关键作用提供了理论依据。
在此,我们对由154例特征明确的人类乳腺癌肿瘤组成的组织微阵列进行了IKKε表达的免疫组化检测。我们进一步确定了其与多个临床病理参数以及5年总生存率、无病生存率和远处无病生存率的相关性。
我们在60.4%的乳腺癌肿瘤中观察到IKKε的表达。IKKε表达状态与用于肿瘤分子分类的一组标志物(包括雌激素受体/孕激素受体/人表皮生长因子受体2状态)或分子亚型均无关联。然而,IKKε表达与淋巴结转移状态呈负相关(p = 0.0032)。此外,我们发现IKKε与表皮生长因子受体表达之间存在新的关联(p = 0.0011)。
IKKε与淋巴结转移呈负相关这一意外发现,促使对原发性乳腺癌进行更大规模的免疫组化分析,以阐明IKKε在转移中的作用。本研究表明,表达表皮生长因子受体和IKKε的乳腺癌肿瘤可能是旨在抑制IKKε活性或表达的药物的潜在靶点。