University of Tuebingen Medical Center II, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
BMC Cancer. 2011 Jan 28;11:42. doi: 10.1186/1471-2407-11-42.
The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients.
Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for SOX2, NANOG and OCT4 gene expression by real-time PCR.
SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432).
In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.
SRY 相关 HMG 盒家族转录因子成员 SOX2 主要在胚胎干细胞以及早期前肠和神经发育中进行研究。最近，SOX2 被证明参与了成体体细胞向多能干细胞状态的重编程，并参与了各种器官的肿瘤发生。在乳腺癌中，SOX2 的表达被报道为基底样肿瘤的特征。在这项研究中，我们评估了 95 例绝经后乳腺癌患者的 95 例原发性肿瘤中的 SOX2 表达。
对蒂宾根大学病理研究所和妇女医院诊断和治疗的 95 例患者的样本进行免疫组织化学分析，以检测原发性肿瘤样本和存在的相应淋巴结转移中的 SOX2 表达。此外，通过 FISH 在代表性样本中评估 SOX2 扩增状态。此外，通过实时 PCR 分析 18 个新鲜冷冻样本中的 SOX2、NANOG 和 OCT4 基因表达。
SOX2 表达在 28%的浸润性乳腺癌和 44%的导管原位癌（DCIS）病变中均有检测到。定义了 SOX2 表达评分（评分 0 至 3），以区分 SOX2 阴性（评分 0）和 SOX2 阳性样本（评分 1-3），后者的亚组为 SOX2 高表达者（评分 3>50%阳性细胞）。总体而言，SOX2 表达（评分 1-3）的发生率高于先前在一组淋巴结阴性患者中的报道（28%比 16.7%）。SOX2 表达在不同的乳腺癌亚型中均有检测到，与肿瘤分级无关。然而，高 SOX2 表达（评分 3）与更大的肿瘤大小（p = 0.047）和阳性淋巴结状态相关（p = 0.018）。相应的转移性淋巴结显示出更高的 SOX2 表达，并且明显比原发性肿瘤更常呈 SOX2 阳性（p = 0.0432）。
在本报告中，我们表明胚胎干细胞因子 SOX2 在各种早期绝经后乳腺癌和转移性淋巴结中表达。我们的数据表明，SOX2 在乳腺癌发生的早期发挥作用，高表达可能促进转移潜能。需要进一步研究来探索 SOX2 是否可以在早期肿瘤阶段预测转移潜能。
