Lower Silesian Centre of Oncology, Wrocław, Poland.
Histol Histopathol. 2013 Apr;28(4):513-24. doi: 10.14670/HH-28.513. Epub 2013 Jan 31.
S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.
S100P-低分子量酸性蛋白已被证明参与多种人类恶性肿瘤的增殖、存活、血管生成、多药耐药和转移过程。在乳腺癌中，S100P 的表达与肿瘤细胞的永生化和侵袭性肿瘤行为相关，表明该蛋白可能具有不良的预后价值。我们分析了 85 例 II 期乳腺癌患者的核和细胞质 S100P 表达，中位随访时间为 17 年。使用针对 S100P 的单克隆抗体对原发肿瘤的石蜡切片进行免疫组织化学反应。我们还使用 KM plotter 研究了 S100P mRNA 表达的预后价值，该分析评估了 22,277 个基因对 2422 例乳腺癌患者生存的影响。此外，还检查了 S100P 在四种乳腺癌细胞系中的表达与细胞对 11 种最常用细胞毒性药物的敏感性之间的关系。单变量和多变量分析表明，核 S100P（S100Pn）的高表达是总生存期和无病时间较短的典型表现。KM plotter 分析表明，S100P 表达升高是无复发生存和无远处转移生存的特异性表现。未发现 S100P 表达与乳腺癌细胞对细胞毒药物的敏感性之间存在关系。我们证明了高 S100Pn 表达水平与早期乳腺癌患者的不良生存相关。由于初步数据表明 S100P 的表达受糖皮质激素受体激活上调，并且几种药物具有激活或抑制 S100P 启动子活性的潜力，因此该蛋白可能成为治疗靶点，并需要进一步研究其在预后、预测和潜在治疗价值方面的作用。
