Department of Obstetrics and Gynecology, Goethe University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurter, Germany.
J Cancer Res Clin Oncol. 2013 Oct;139(10):1681-9. doi: 10.1007/s00432-013-1490-5. Epub 2013 Aug 18.
Sphingolipids play important roles in apoptosis and cell proliferation. Sphingosine kinase 1 (SphK1) expression has a prognostic impact in primary breast cancer, but its predictive value is currently unknown.
A total of 112 breast cancer specimens from a prospective neoadjuvant chemotherapy trial (GeparDuo) were studied. Using tissue microarrays of pre-treatment core cut biopsies, we determined the expression of SphK1 by immunohistochemistry. The upper quartile of the cohort according to an immune reactive score of SphK1 was used as cutoff for high expression.
We observed a larger number of samples with high SphK1 expression among ER-negative cancers (36.8 vs. 20.5 % among ER-positive cancers; Fisher test p = 0.073). Eighteen of the 112 patients demonstrated a pathological complete response. A significant predictive value for pathological complete response was observed for ER negativity (p = 0.003), young age (p = 0.037), and high tumor grade (p = 0.049). An increased pCR rate was observed in tumors with high SphK1 expression within the luminal subtype (26.7 vs. 5.8 %; Fisher test p = 0.040). No significant difference in survival was detected according to SphK1 expression.
Our results suggest that SphK1 may be a predictive factor for pCR after neoadjuvant treatment in luminal type breast cancers and warrants further investigation.
神经酰胺在细胞凋亡和增殖中发挥重要作用。在原发性乳腺癌中，鞘氨醇激酶 1（SphK1）的表达具有预后影响，但目前其预测价值尚不清楚。
对一项前瞻性新辅助化疗试验（GeparDuo）的 112 例乳腺癌标本进行了研究。使用预处理核心切活检的组织微阵列，通过免疫组织化学测定 SphK1 的表达。根据 SphK1 的免疫反应评分，将队列的上四分位数作为高表达的截止值。
我们观察到 ER 阴性癌症中高 SphK1 表达的样本数量较多（ER 阳性癌症中为 36.8%，ER 阴性癌症中为 20.5%；Fisher 检验，p = 0.073）。112 例患者中有 18 例发生了病理完全缓解。病理完全缓解的预测价值与 ER 阴性（p = 0.003）、年龄较小（p = 0.037）和肿瘤分级较高（p = 0.049）显著相关。在 luminal 型肿瘤中，高 SphK1 表达的肿瘤 pCR 率较高（26.7%比 5.8%；Fisher 检验，p = 0.040）。但根据 SphK1 表达，并未检测到生存的显著差异。
我们的结果表明，SphK1 可能是新辅助治疗后 luminal 型乳腺癌 pCR 的预测因素，值得进一步研究。
