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.
Highlights
Ovarian cancer, consisting mainly of ovarian carcinoma (OC), is the 7th most common cancer and the 8th most common cause of cancer death in women
ATRX and DAXX are frequently expressed in high-grade serous carcinoma (HGSC) effusions
ATRX and DAXX were expressed in HGSC cells in 386/400 (96%) and 348/400 (87%) effusions, respectively
Summary
Ovarian cancer, consisting mainly of ovarian carcinoma (OC), is the 7th most common cancer and the 8th most common cause of cancer death in women. Overall survival (OS) is currently longer than previously, with approximately 45% of patients alive at 5 years, due to improved surgery and chemotherapy protocols, as well as targeted therapy. This figure is true for all histological types combined. In high-grade serous carcinoma (HGSC), the most common and Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway. Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway aggressive type of OC, diagnosis is often at advanced-stage (FIGO stage III–IV) and death-of-disease occurs in the majority of patients [1]. Better understanding of the molecular profile of cancer cells in effusions is an important challenge
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
