Pinto Filipe, Campanella Nathalia C, Abrahão-Machado Lucas F, Scapulatempo-Neto Cristovam, de Oliveira Antonio T, Brito Maria J, Andrade Raquel P, Guimarães Denise P, Reis Rui M
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Gastric Cancer. 2016 Apr;19(2):651-659. doi: 10.1007/s10120-015-0505-0. Epub 2015 May 21.
The T-box transcription factor Brachyury was recently reported to be upregulated and associated with prognosis in solid tumors. Here, we proposed to evaluate the potential use of Brachyury protein expression as a new prognostic biomarker in gastrointestinal stromal tumors (GIST).
Brachyury protein expression was analyzed by immunohistochemistry in a cohort of 63 bona fide GIST patients. Brachyury expression profiles were correlated with patients' clinicopathological features and prognostic impact. Additionally, an in silico analysis was performed using the Oncomine database to assess Brachyury alterations at DNA and mRNA levels in GISTs.
We found that Brachyury was overexpressed in the majority (81.0 %) of primary GISTs. We observed Brachyury staining in the nucleus alone in 4.8 % of cases, 23.8 % depicted only cytoplasm staining, and 52.4 % of cases exhibited both nucleus and cytoplasm immunostaining. The presence of Brachyury was associated with aggressive GIST clinicopathological features. Particularly, Brachyury nuclear (with or without cytoplasm) staining was associated with the presence of metastasis, while cytoplasm sublocalization alone was correlated with poor patient survival.
Herein, we demonstrate that Brachyury is overexpressed in GISTs and is associated with worse outcome, constituting a novel prognostic biomarker and a putative target for GIST treatment.
T盒转录因子Brachyury最近被报道在实体瘤中表达上调且与预后相关。在此，我们旨在评估Brachyury蛋白表达作为胃肠道间质瘤（GIST）一种新的预后生物标志物的潜在用途。
采用免疫组织化学方法分析63例确诊GIST患者队列中Brachyury蛋白的表达情况。将Brachyury表达谱与患者的临床病理特征及预后影响相关联。此外，利用Oncomine数据库进行电子分析，以评估GIST中DNA和mRNA水平的Brachyury改变情况。
我们发现大多数（81.0%）原发性GIST中Brachyury过表达。我们观察到，4.8%的病例中Brachyury仅在细胞核中染色，23.8%的病例仅表现为细胞质染色，52.4%的病例同时出现细胞核和细胞质免疫染色。Brachyury的存在与侵袭性GIST临床病理特征相关。特别是，Brachyury细胞核（有或无细胞质）染色与转移的存在相关，而仅细胞质定位与患者预后不良相关。
在此，我们证明Brachyury在GIST中过表达且与较差的预后相关，构成一种新的预后生物标志物及GIST治疗的潜在靶点。
