Golouh Rastko, Cufer Tanja, Sadikov Aleksander, Nussdorfer Petra, Usher Pernille Autzen, Brünner Nils, Schmitt Manfred, Lesche Ralf, Maier Sabine, Timmermans Mieke, Foekens John A, Martens John W M
Institute of Oncology, Ljubljana, Slovenia.
Breast Cancer Res Treat. 2008 Jul;110(2):317-26. doi: 10.1007/s10549-007-9724-3. Epub 2007 Sep 13.
We recently found that DNA methylation of S100A2, spleen tyrosine kinase (SYK), and Stathmin-1 (STMN1) correlates with response to tamoxifen therapy in metastatic breast cancer. In this retrospective study, we investigated immunohistochemically whether these three markers are predictors of relapse in early breast cancer (EBC) patients treated with adjuvant tamoxifen alone.
Immunohistochemical staining was performed for S100A2, SYK and STMN1 on a tissue microarray containing ER-positive invasive breast carcinomas from a study cohort of 215 operable breast cancer patients, who underwent radical local therapy and who were treated with adjuvant tamoxifen monotherapy. Cox regression was used to correlate staining intensity of the three markers with main endpoints in our study; disease-free survival (DFS), and disease-specific survival (DSS).
In univariate analysis, only STMN1 staining intensity strongly correlated with DFS (P = 0.014) and DSS (P = 0.002). In the groups of low and high STMN1 intensity, DFS was 84% and 63%, and DSS was 89% and 70%. STMN1 retained its prognostic value for DFS (P = 0.002) and DSS (<0.001) in the multivariate model together with lymph node status. We found also a trend to better DFS in patients with low STMN1 intensity in both lymph node-positive (P = 0.001) and -negative patients (P = 0.065). As the tumour cells did not express S100A2 (except in one case) the potential prognostic value of this marker was not evaluated.
Staining intensity of STMN1, but not SYK, predicted outcome in our collective of ER- positive tamoxifen treated EBC patients.
我们最近发现，S100A2、脾酪氨酸激酶（SYK）和Stathmin-1（STMN1）的DNA甲基化与转移性乳腺癌患者对他莫昔芬治疗的反应相关。在这项回顾性研究中，我们通过免疫组织化学方法研究了这三种标志物是否为单纯接受辅助性他莫昔芬治疗的早期乳腺癌（EBC）患者复发的预测指标。
对来自215例可手术乳腺癌患者研究队列的组织芯片进行S100A2、SYK和STMN1免疫组织化学染色，这些患者接受了根治性局部治疗并接受辅助性他莫昔芬单一疗法。采用Cox回归分析将这三种标志物的染色强度与我们研究中的主要终点进行关联；无病生存期（DFS）和疾病特异性生存期（DSS）。
在单因素分析中，只有STMN1染色强度与DFS（P = 0.014）和DSS（P = 0.002）密切相关。在STMN1低强度和高强度组中，DFS分别为84%和63%，DSS分别为89%和70%。在多因素模型中，STMN1与淋巴结状态一起对DFS（P = 0.002）和DSS（<0.001）仍具有预后价值。我们还发现，在淋巴结阳性（P = 0.001）和阴性患者（P = 0.065）中，STMN1低强度患者的DFS有更好的趋势。由于肿瘤细胞不表达S100A2（仅1例除外），因此未评估该标志物的潜在预后价值。
在我们接受他莫昔芬治疗的ER阳性EBC患者群体中，STMN1的染色强度而非SYK能够预测预后。
