Waldmann J, Feldmann G, Slater E P, Langer P, Buchholz M, Ramaswamy A, Saeger W, Rothmund M, Fendrich V
Department of Surgery, Philipps-Universität Marburg, Marburg, Germany.
Br J Cancer. 2008 Dec 2;99(11):1900-7. doi: 10.1038/sj.bjc.6604755. Epub 2008 Nov 18.
In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT-PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time-PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.
在本研究中，我们评估了Snail在肾上腺皮质癌（ACC）中是否表达，以及其表达是否与患者预后相关。锌指转录因子Snail最广为人知的功能之一是诱导上皮-间质转化（EMT）。越来越多的证据表明，EMT在肿瘤进展和转移扩散中起关键作用。通过免疫组织化学评估了26例切除的ACC中Snail和E-钙黏蛋白的表达，并进行了实时定量RT-PCR表达分析。数据与临床结果相关，特别是与患者总生存期相关。通过免疫组织化学评估时，26个ACC肿瘤样本中有17个（65%）表达Snail。在正常肾上腺皮质组织和良性肾上腺皮质腺瘤中均未检测到Snail表达。通过实时PCR在mRNA水平上证实了表达水平。与Snail阴性肿瘤相比，Snail阳性肿瘤的生存率显著降低：在分别进行了14.5个月和28.5个月的中位随访后，16例患者中有10例、8例患者中有1例死于疾病（P=0.03）。表达Snail的ACC患者多为晚期疾病（12例中有11例 vs 14例中有6例，P=0.01），并且与染色阴性的患者相比，更容易发生远处转移（11例中有7例 vs 8例中有2例，P=0.19）。总之，我们首次描述了Snail在大部分ACC中表达。此外，Snail表达与生存率降低、疾病晚期以及发生远处转移的较高风险相关。
