Death domain-associated protein (DAXX) expression is associated with poor survival in metastatic high-grade serous carcinoma.
Virchows Arch
; 477(6): 857-864, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32533344
ABSTRACT
The objective of this study was to analyze the expression and clinical role of mitosis regulators α-thalassemia/mental retardation syndrome X-linked (ATRX) and death-domain-associated protein (DAXX) in metastatic high-grade serous carcinoma (HGSC). ATRX and DAXX protein expression by immunohistochemistry was analyzed in 400 HGSC effusions. DAXX expression was additionally studied in 15 cancer cell lines, including 4 ovarian carcinoma lines, and in 81 of the 400 HGSC effusions using Western blotting. ATRX and DAXX were expressed in HGSC cells in 386/400 (96%) and 348/400 (87%) effusions, respectively. Western blotting showed DAXX expression in all 15 cell lines and in 70/81 (86%) HGSC effusions. DAXX expression by immunohistochemistry was higher in pleural compared to peritoneal effusions (p = 0.006) and in post-chemotherapy compared to pre-chemotherapy effusions (p = 0.004), and its expression was significantly associated with poor overall survival in univariate of the entire cohort (p = 0.014), as well as analysis limited to chemo-naïve effusions tapped at diagnosis (p = 0.038). The former association retained its prognostic role in Cox multivariate survival analysis (p = 0.011). ATRX expression was unrelated to clinicopathologic parameters or survival. In conclusion, DAXX is associated with disease progression and could be a prognostic marker in metastatic HGSC. Silencing this molecule may have therapeutic relevance in this cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Biomarcadores de Tumor
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Cistadenocarcinoma Seroso
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Chaperonas Moleculares
/
Proteínas Co-Represoras
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
/
Aged80
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Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Virchows Arch
Asunto de la revista:
BIOLOGIA MOLECULAR
/
PATOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Noruega