Buentzel Judith, Yao Sha, Elakad Omar, Lois Anna-Maria, Brünies Jana, König Julia, Hinterthaner Marc, Danner Bernhard C, Ströbel Philipp, Emmert Alexander, Bohnenberger Hanibal
Department of Hematology and Medical Oncology.
Institute of Pathology.
Medicine (Baltimore). 2019 Aug;98(31):e16712. doi: 10.1097/MD.0000000000016712.
Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with operable lung cancer disease.The protein abundance (in the following text also named protein expression) of ATRX and DAXX were analyzed by immunohistochemistry in 194 samples of squamous cell lung carcinoma (SQCLC), 111 samples of pulmonary adenocarcinoma (AC) and 40 samples of small cell lung cancer (SCLC). The protein levels of ATRX and DAXX were correlated with clinicopathological characteristics and patient outcome.ATRX showed strong protein expression in 16.2% of AC, 11.9% of SQCLC, and 42.5% of SCLC. DAXX was highly expressed in 54.9% of AC, 76.2% of SQCLC, and 82.5% of SCLC. Immunostaining of both ATRX and DAXX were seen in 14.4% of AC, 11.3% of SQCLC, and 42.5% of SCLC. High protein expression of ATRX was a favorable prognostic marker for patients with AC (hazard ratio 0.38, P = .02). Sub-group analyses showed a significant correlation between ATRX and the clinical stage of SQCLC and SCLC. Histological grading and ATRX were also significantly associated in cases of SQCLC.The presence of ATRX and DAXX are correlated with lung cancer histology. Strong ATRX protein expression is associated with a significantly longer overall survival in patients with AC.
肺癌根治术后标本的分子特征可提供额外的预后信息,并可能有助于指导辅助治疗程序。转录调节因子α地中海贫血/智力发育迟缓X连锁(ATRX)和死亡结构域相关蛋白(DAXX)最近在不同癌症实体中被描述为一种有用的预后生物标志物。本研究旨在探讨它们在可手术肺癌患者中的蛋白表达模式及预后价值。通过免疫组织化学分析了194例肺鳞状细胞癌(SQCLC)、111例肺腺癌(AC)和40例小细胞肺癌(SCLC)样本中ATRX和DAXX的蛋白丰度(以下文本中也称为蛋白表达)。ATRX和DAXX的蛋白水平与临床病理特征及患者预后相关。ATRX在16.2%的AC、11.9%的SQCLC和42.5%的SCLC中显示出强蛋白表达。DAXX在54.9%的AC、76.2%的SQCLC和82.5%的SCLC中高表达。在14.4%的AC、11.3%的SQCLC和42.5%的SCLC中同时观察到ATRX和DAXX的免疫染色。ATRX的高蛋白表达是AC患者的良好预后标志物(风险比0.38,P = 0.02)。亚组分析显示ATRX与SQCLC和SCLC的临床分期之间存在显著相关性。在SQCLC病例中,组织学分级与ATRX也显著相关。ATRX和DAXX的存在与肺癌组织学相关。AC患者中,ATRX强蛋白表达与显著更长的总生存期相关。