Mumm Jan-Niclas, Kölbl Alexandra C, Jeschke Udo, Andergassen Ulrich
Department of Obstetrics and Gynaecology, Ludwig-Maximilians University of Munich, Munich, Germany.
Onco Targets Ther. 2016 May 26;9:3163-9. doi: 10.2147/OTT.S101677. eCollection 2016.
Triple-negative breast cancer (TNBC) is a rather aggressive form of breast cancer, comprised by early metastasis formation and reduced overall survival of the affected patients. Steroid hormone receptors and the human epidermal growth factor receptor 2 are not overexpressed, limiting therapeutic options. Therefore, new treatment options have to be investigated. The aim of our preliminary study was to detect coherences between some molecules of intracellular signal transduction pathways and survival of patients with TNBC, in order to obtain some hints for new therapeutical solutions.
Thirty-one paraffin-embedded tumor tissue samples, which were determined to be negative for steroid hormone receptors as well as human epidermal growth factor receptor 2, were immunohistochemically stained for a number of signal transduction molecules from several signaling pathways. β-Catenin, HIF1α, MCL, Notch1, LRP6, XBP1, and FOXP3 were stained with specific antibodies, and their staining was correlated with patient survival by Kaplan-Meier analyses.
Only two of the investigated molecules have shown correlation with overall survival. Cytoplasmic staining of HIF1α and centro-tumoral lymphocyte FOXP3 staining showed statistically significant correlations with survival.
The coherence of signal transduction molecules with survival of patients with TNBC is still controversially discussed in the literature. Our study comprises one more mosaic stone in the elucidation of these intracellular processes and their influences on patient outcome. Lots of research still has to be done in this field, but it would be worthwhile as it may offer new therapeutic targets for a group of patients with breast cancer, which is still hard to treat.
三阴性乳腺癌（TNBC）是一种侵袭性较强的乳腺癌，其特点是早期发生转移且患者总体生存率降低。类固醇激素受体和人表皮生长因子受体2未过度表达，限制了治疗选择。因此，必须研究新的治疗方案。我们初步研究的目的是检测细胞内信号转导通路的一些分子与TNBC患者生存率之间的相关性，以便为新的治疗方案提供一些线索。
对31份石蜡包埋的肿瘤组织样本进行免疫组织化学染色，这些样本经检测类固醇激素受体和人表皮生长因子受体2均为阴性，检测多种信号转导通路中的一些信号转导分子。用特异性抗体对β-连环蛋白、低氧诱导因子1α（HIF1α）、髓细胞白血病-1（MCL）、Notch1、低密度脂蛋白受体相关蛋白6（LRP6）、X盒结合蛋白1（XBP1）和叉头框蛋白P3（FOXP3）进行染色，并通过Kaplan-Meier分析将它们的染色与患者生存率相关联。
仅两种被研究分子显示出与总体生存率相关。HIF1α的细胞质染色和肿瘤中心淋巴细胞FOXP3染色与生存率显示出统计学上的显著相关性。
信号转导分子与TNBC患者生存率之间的相关性在文献中仍存在争议。我们的研究为阐明这些细胞内过程及其对患者预后的影响增添了一块拼图。该领域仍有大量研究要做，但这是值得的，因为它可能为一组仍难以治疗的乳腺癌患者提供新的治疗靶点。
