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Brachyury oncogene is a prognostic factor in high‐risk testicular germ cell tumors
Author(s) -
Pinto F.,
Cárcano F. M.,
Silva E. C. A.,
Vidal D. O.,
ScapulatempoNeto C.,
Lopes L. F.,
Reis R. M.
Publication year - 2018
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12495
Subject(s) - brachyury , germ cell tumors , germ cell , biology , tissue microarray , cancer research , immunohistochemistry , pathology , metastasis , cancer , medicine , embryonic stem cell , immunology , mesoderm , biochemistry , genetics , chemotherapy , gene
Summary The T‐box transcription factor Brachyury has been considered a cancer‐specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial–mesenchymal transition, metastasis, and poor prognosis. However, its clinical association with testicular germ cell tumor is unknown. We analyzed the expression of Brachyury by immunohistochemistry in a series of well‐characterized testicular germ cell tumor samples and at transcript level by in silico analysis. Additionally, we aimed to investigate the clinical significance of Brachyury in testicular germ cell tumor. Brachyury cytoplasm immunostaining was present in 89.6% (86/96) of cases with nuclear staining observed in 24% (23/96) of testicular germ cell tumor. Bioinformatics microarray expression analysis of two independent cohorts of testicular germ cell tumors showed similar results with increased levels of Brachyury in testicular germ cell tumors and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with lower event‐free survival ( p = 0.04) and overall survival ( p = 0.01) in intermediate/high‐risk testicular germ cell tumors. Univariate analysis showed that Brachyury nuclear subcellular localization was a predictor of poor prognosis ( p = 0.02), while a tendency was observed by multivariate analysis (HR: 3.56, p = 0.06). In conclusion, these results indicate that Brachyury plays an oncogenic role in testicular germ cell tumors and its subcellular localization in the nucleus may constitute a novel biomarker of poor prognosis and a putative oncotarget for intermediate/high‐risk testicular germ cell tumor patients.