Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Breast Cancer Res Treat. 2010 Oct;123(3):733-45. doi: 10.1007/s10549-009-0672-y. Epub 2009 Dec 18.
Chemokine receptor CXCR4 is known to be crucially involved in tumor progression, but the role of its ligand, stromal cell-derived factor-1 (SDF-1), remains unclear. The present study was conducted to clarify the clinicopathological and prognostic impact of SDF-1 expression in invasive breast cancers. Expression of SDF-1 mRNA and protein was examined in five breast cancer cell lines with or without estradiol treatment. In 52 surgically resected breast cancers, the level of SDF-1 mRNA in frozen samples and the pattern of SDF-1 protein immunoreactivity in formalin-fixed paraffin-embedded tissue sections were compared. In another cohort of 223 breast cancers, the correlation between SDF-1 immunoreactivity and clinicopathological parameters was examined using a tissue microarray. Estradiol treatment markedly increased the expression of SDF-1 mRNA and protein in the estrogen receptor (ER)-positive cell lines, MCF-7 and T47D. Among the 52 resected breast cancers, those with a cytoplasmic-dominant pattern of SDF-1 expression showed higher SDF-1 mRNA levels (median 27.4) than those with a membrane-dominant or negative pattern (median 13.6, P = 0.0017). Accordingly, the cytoplasmic-dominant pattern was defined as "high SDF-1 expression," and other patterns were defined as "low SDF-1 expression." Among the cohort of 223 tumors, "high SDF-1 expression" was detected in 158 (70.9%) and was significantly correlated with ER positivity (P < 0.0001), HER2 negativity (P = 0.021), and lower grade (P < 0.0001). Univariate analysis demonstrated that "high SDF-1 expression" was a significant indicator of better clinical outcome in both the entire patient cohort (P = 0.017) and the 133 patients with ER-positive tumors (P = 0.036), but not in the 90 patients with ER-negative tumors. Multivariate analysis showed that SDF-1 status was an independent factor related to overall survival in patients with ER-positive tumors (P = 0.046). SDF-1 status is a significant prognostic factor and may be clinically useful for assigning adjuvant therapy to patients with ER-positive invasive breast cancers.
趋化因子受体 CXCR4 已知在肿瘤进展中起着至关重要的作用，但配体基质细胞衍生因子-1（SDF-1）的作用仍不清楚。本研究旨在阐明 SDF-1 在浸润性乳腺癌中的临床病理和预后影响。使用经或未经雌二醇处理的五种乳腺癌细胞系检测 SDF-1mRNA 和蛋白的表达。在 52 例手术切除的乳腺癌中，比较了冷冻样本中 SDF-1mRNA 的水平和福尔马林固定石蜡包埋组织切片中 SDF-1 蛋白免疫反应的模式。在另一队列的 223 例乳腺癌中，使用组织微阵列检查了 SDF-1 免疫反应与临床病理参数之间的相关性。雌二醇处理明显增加了雌激素受体（ER）阳性细胞系 MCF-7 和 T47D 中 SDF-1mRNA 和蛋白的表达。在 52 例切除的乳腺癌中，具有细胞质主导型 SDF-1 表达模式的患者 SDF-1mRNA 水平较高（中位数 27.4），而具有膜主导型或阴性模式的患者 SDF-1mRNA 水平较低（中位数 13.6，P = 0.0017）。因此，细胞质主导型被定义为“高 SDF-1 表达”，其他模式被定义为“低 SDF-1 表达”。在 223 例肿瘤队列中，检测到 158 例（70.9%）存在“高 SDF-1 表达”，并且与 ER 阳性（P < 0.0001）、HER2 阴性（P = 0.021）和较低的分级（P < 0.0001）显著相关。单因素分析表明，在整个患者队列（P = 0.017）和 133 例 ER 阳性肿瘤患者（P = 0.036）中，“高 SDF-1 表达”是临床结局较好的显著指标，但在 90 例 ER 阴性肿瘤患者中并非如此。多因素分析显示，SDF-1 状态是 ER 阳性肿瘤患者总生存的独立相关因素（P = 0.046）。SDF-1 状态是一个重要的预后因素，对于为 ER 阳性浸润性乳腺癌患者分配辅助治疗可能具有临床意义。
