Davidson Ben, Holth Arild, Wang Zhihui, Hellsylt Ellen, Tropé Claes G, Hetland Falkenthal Thea E, Holm Ruth
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
APMIS. 2018 Apr;126(4):309-313. doi: 10.1111/apm.12816. Epub 2018 Feb 21.
The objective of this study was to analyze the expression and clinical role of 14-3-3 family proteins in high-grade serous carcinoma (HGSC). Protein expression of 14-3-3 sigma (14-3-3σ) and 14-3-3 eta (14-3-3η) by immunohistochemistry was studied in 298 HGSC specimens (249 peritoneal, 49 pleural) and was analyzed for association with clinicopathologic parameters, chemoresponse and survival. The 14-3-3σ protein was diffusely (>75% of cells) expressed in 100% of carcinomas in analysis of a pilot series and was therefore not further analyzed. The 14-3-3η protein was expressed to a variable extent in 260/298 (87%) effusions. Higher 14-3-3η protein expression was significantly related to higher CA 125 levels at diagnosis (p = 0.004), but was unrelated to other clinicopathologic parameters, chemoresponse or survival. Analysis of the association between 14-3-3η and previously studied proteins regulating mitosis showed positive association with class III β-tubulin expression (p = 0.025). The present study documents frequent expression of 14-3-3σ and 14-3-3η in HGSC effusions, but does not support a role for these proteins as prognostic markers or predictors of chemotherapy response in metastatic HGSC.
本研究的目的是分析14-3-3家族蛋白在高级别浆液性癌(HGSC)中的表达及临床作用。通过免疫组织化学研究了298例HGSC标本(249例腹膜癌、49例胸膜癌)中14-3-3西格玛(14-3-3σ)和14-3-3伊塔(14-3-3η)的蛋白表达,并分析其与临床病理参数、化疗反应和生存率的相关性。在一个先导系列分析中,100%的癌组织中14-3-3σ蛋白呈弥漫性(>75%的细胞)表达,因此未进一步分析。14-3-3η蛋白在260/298(87%)的积液中呈不同程度表达。14-3-3η蛋白高表达与诊断时较高的CA 125水平显著相关(p = 0.004),但与其他临床病理参数、化疗反应或生存率无关。分析14-3-3η与先前研究的调节有丝分裂的蛋白之间的关联,发现其与III类β-微管蛋白表达呈正相关(p = 0.025)。本研究记录了HGSC积液中14-3-3σ和14-3-3η的频繁表达,但不支持这些蛋白作为转移性HGSC预后标志物或化疗反应预测指标的作用。