University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA.
University of Michigan School of Public Health, Department of Biostatistics, Ann Arbor, MI, USA.
Breast Cancer Res Treat. 2017 Nov;166(1):85-94. doi: 10.1007/s10549-017-4366-6. Epub 2017 Jul 17.
Elevated S100A8 expression has been observed in cancers of the bladder, esophagus, colon, ovary, and breast. S100A8 is expressed by breast cancer cells as well as by infiltrating immune and myeloid cells. Here we investigate the association of elevated S100A8 protein expression in breast cancer cells and in breast tumor stroma with survival outcomes in a cohort of breast cancer patients.
Tissue microarrays (TMA) were constructed from breast cancer specimens from 417 patients with stage I-III breast cancer treated at the University of Michigan Comprehensive Cancer Center between 2004 and 2006. Representative regions of non-necrotic tumor and distant normal tissue from each patient were used to construct the TMA. Automated quantitative immunofluorescence (AQUA) was used to measure S100A8 protein expression, and samples were scored for breast cancer cell and stromal S100A8 expression. S100A8 staining intensity was assessed as a continuous value and by exploratory dichotomous cutoffs. Associations between breast cancer cell and stromal S100A8 expression with disease-free survival and overall survival were determined using the Kaplan-Meier method and Cox proportional hazard models.
High breast cancer cell S100A8 protein expression (as indicated by AQUA scores), as a continuous measure, was a significant prognostic factor for OS [univariable hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.00-1.55, p = 0.05] in this patient cohort. Exploratory analyses identified optimal S100A8 AQUA score cutoffs within the breast cancer cell and stromal compartments that significantly separated survival curves for the complete cohort. Elevated breast cancer cell and stromal S100A8 expression, indicated by higher S100A8 AQUA scores, significantly associates with poorer breast cancer outcomes, regardless of estrogen receptor status.
Elevated breast cancer cell and stromal S1008 protein expression are significant indicators of poorer outcomes in early stage breast cancer patients. Evaluation of S100A8 protein expression may provide additional prognostic information beyond traditional breast cancer prognostic biomarkers.
已观察到 S100A8 在膀胱癌、食管癌、结肠癌、卵巢癌和乳腺癌中的表达升高。乳腺癌细胞以及浸润的免疫细胞和髓样细胞均表达 S100A8。在这里，我们研究了乳腺癌细胞和乳腺癌肿瘤基质中 S100A8 蛋白表达升高与密歇根大学综合癌症中心在 2004 年至 2006 年间治疗的 I-III 期乳腺癌患者队列生存结果之间的关联。
从 417 例患有 I-III 期乳腺癌的密歇根大学综合癌症中心患者的乳腺癌标本中构建组织微阵列（TMA）。使用每个患者的非坏死肿瘤和远处正常组织的代表性区域来构建 TMA。自动定量免疫荧光（AQUA）用于测量 S100A8 蛋白表达，并对乳腺癌细胞和基质 S100A8 表达进行评分。S100A8 染色强度作为连续值和探索性二分截止值进行评估。使用 Kaplan-Meier 方法和 Cox 比例风险模型确定乳腺癌细胞和基质 S100A8 表达与无病生存和总生存之间的关系。
高乳腺癌细胞 S100A8 蛋白表达（如 AQUA 评分所示），作为连续指标，是该患者队列 OS 的显著预后因素[单变量危险比（HR）1.24，95%置信区间（CI）1.00-1.55，p=0.05]。探索性分析确定了乳腺癌细胞和基质区室中 S100A8 AQUA 评分的最佳截断值，这些截断值显著分离了整个队列的生存曲线。升高的乳腺癌细胞和基质 S100A8 表达，表现为更高的 S100A8 AQUA 评分，与乳腺癌结局较差显著相关，而与雌激素受体状态无关。
升高的乳腺癌细胞和基质 S1008 蛋白表达是早期乳腺癌患者预后不良的重要指标。S100A8 蛋白表达的评估可能提供比传统乳腺癌预后生物标志物更多的预后信息。
