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

Autor(es)

Pinto, Filipe ^{[1, 2]} ; Campanella, Nathalia C. ^[3] ; Abrahao-Machado, Lucas F. ^[4] ; Scapulatempo-Neto, Cristovam ^{[3, 4]} ; de Oliveira, Antonio T. ^{[3, 5]} ; Brito, Maria J. ^[6] ; Andrade, Raquel P. ^[7] ; Guimaraes, Denise P. ^{[3, 8]} ; Reis, Rui M. ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[2] ICVS 3Bs PT Govt Associate Lab, Braga, Guimaraes - Portugal

^[3] Barretos Canc Hosp, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

^[4] Barretos Canc Hosp, Dept Pathol, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

^[5] Barretos Canc Hosp, Upper Digest Surg Dept, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

^[6] Hosp Garcia de Orta, Dept Pathol, Almada - Portugal

^[7] Univ Algarve, Dept Med & Biomed Sci, Regenerat Med Program, Faro - Portugal

^[8] Barretos Canc Hosp, Dept Endoscopy, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: GASTRIC CANCER; v. 19, n. 2, p. 651-659, APR 2016.
• Citações Web of Science: 8

Resumo

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. (AU)

• Processo FAPESP: 13/25787-3 - Estudo de biomarcadores de prognóstico e resposta terapêutica em tumores estromais gastrointestinais (GISTs)
• Beneficiário: Nathália Cristina Campanella
• Linha de fomento: Bolsas no Brasil - Doutorado Direto