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.

这项研究的目的是分析有丝分裂调节剂α地中海贫血/智力低下综合征X连锁（ATRX）和死亡域相关蛋白（DAXX）在转移性高度浆液性癌（HGSC）中的表达及其临床作用。在400 HGSC渗出液中通过免疫组织化学分析了ATRX和DAXX蛋白的表达。此外，还使用Western印迹法在15种癌细胞系（包括4种卵巢癌细胞系）和400种HGSC积液中的81种中研究了DAXX的表达。ATRX和DAXX在HGSC细胞中分别以386/400（96％）和348/400（87％）的积液表达。蛋白质印迹显示在所有15个细胞系和70/81（86％）HGSC积液中DAXX表达。与腹膜积液相比，免疫组化法检测的DAXX表达较高（p = 0.006），并且在化疗后与化疗前的积液相比（p  = 0.004），其表达与整个队列的单变量总体生存率差（p  = 0.014）显着相关，并且分析仅限于化学治疗诊断时发现幼稚的积液（p  = 0.038）。前者在Cox多变量生存分析中保留了其预后作用（p  = 0.011）。ATRX的表达与临床病理参数或生存无关。总之，DAXX与疾病进展有关，可能是转移性HGSC的预后指标。使该分子沉默可能与这种癌症具有治疗意义。