The embryonic Brachyury transcription factor is a novel biomarker of GIST aggressiveness and poor survival.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Pinto|Filipe|F|', 'Campanella|Nathalia C|NC|', 'Abrahão-Machado|Lucas F|LF|', 'Scapulatempo-Neto|Cristovam|C|', 'de Oliveira|Antonio T|AT|', 'Brito|Maria J|MJ|', 'Andrade|Raquel P|RP|', 'Guimarães|Denise P|DP|', 'Reis|Rui M|RM|']
D000368:Aged D014408:Biomarkers, Tumor D002467:Cell Nucleus D003593:Cytoplasm D005260:Female D005326:Fetal Proteins D005770:Gastrointestinal Neoplasms D046152:Gastrointestinal Stromal Tumors D006801:Humans D007150:Immunohistochemistry D008297:Male D008875:Middle Aged D011379:Prognosis D040081:Protein Array Analysis D020825:T-Box Domain Proteins
Brachyury GIST Metastasis Poor prognosis