Davies Helen E, Sadler Ross S, Bielsa Silvia, Maskell Nicholas A, Rahman Najib M, Davies Robert J O, Ferry Berne L, Lee Y C Gary
Oxford Centre for Respiratory Medicine, University of Oxford, Oxford, UK.
Am J Respir Crit Care Med. 2009 Sep 1;180(5):437-44. doi: 10.1164/rccm.200811-1729OC. Epub 2009 Mar 19.
Serum mesothelin is a new biomarker for the diagnosis of mesothelioma. Patients with mesothelioma commonly present with pleural effusions. To define the clinical utility of mesothelin quantification in pleural fluid, we assessed its additional value over pleural fluid cytology and its short-term reproducibility and reliability after pleural inflammatory processes, including pleurodesis.
To assess the diagnostic role of pleural fluid mesothelin and the effect of common clinical factors that may influence measurement accuracy.
Mesothelin was quantified in 424 pleural fluid and 64 serum samples by ELISA. Fluid was collected prospectively from 167 patients who presented with pleural effusions for investigation. Serial pleural fluid samples were obtained from patients (n = 33) requiring repeated drainage. Mesothelin levels were also measured in patients (n = 32) prepleurodesis and postpleurodesis.
Pleural fluid mesothelin concentrations were significantly higher in patients with mesothelioma (n = 24) relative to those with metastatic carcinomas (n = 67) and benign effusions (n = 75): median (interquartile range, 25th-75th percentile) = 40.3 (18.3-68.1) versus 6.1 (1.5-13.2) versus 3.7 (0.0-12.4) nM, respectively, P < 0.0001. Mesothelin measurement was superior to cytological examination in the diagnosis and exclusion of mesothelioma (sensitivity, 71 vs. 35%; specificity, 89 vs. 100%; negative predictive value, 95 vs. 82%, respectively). In patients with "suspicious" cytology, pleural fluid mesothelin was 100% specific for mesothelioma, and in cytology-negative effusions (n = 105) offered a negative predictive value of 94%. Intraindividual reproducibility of pleural fluid mesothelin was excellent: mean (+/-SD) variation, -0.15 (+/-8.41) nM in samples collected within 7 days from patients with mesothelioma. Measurements remained reliable after pleurodesis and were not affected by the presence of bacteria.
Pleural fluid mesothelin provides additional diagnostic value relative to cytological examination. Mesothelin measurements are reproducible and not affected by inflammatory pleural processes.
血清间皮素是诊断间皮瘤的一种新生物标志物。间皮瘤患者通常伴有胸腔积液。为了确定胸腔积液中间皮素定量的临床应用价值，我们评估了其相对于胸腔积液细胞学检查的附加价值，以及在包括胸膜固定术在内的胸膜炎症过程后的短期可重复性和可靠性。
评估胸腔积液间皮素的诊断作用以及可能影响测量准确性的常见临床因素的影响。
采用酶联免疫吸附测定法（ELISA）对424份胸腔积液和64份血清样本中的间皮素进行定量。前瞻性收集了167例因胸腔积液前来检查的患者的积液。对需要反复引流的患者（n = 33）获取系列胸腔积液样本。还对32例患者在胸膜固定术前和术后测量了间皮素水平。
间皮瘤患者（n = 24）胸腔积液中间皮素浓度显著高于转移性癌患者（n = 67）和良性积液患者（n = 75）：中位数（四分位间距，第25 - 75百分位数）分别为40.3（18.3 - 68.1）、6.1（1.5 - 13.2）和3.7（0.0 - 12.4）nM，P < 0.0001。间皮素测量在间皮瘤的诊断和排除方面优于细胞学检查（敏感性分别为71%对35%；特异性分别为89%对100%；阴性预测值分别为95%对82%）。在细胞学“可疑”的患者中，胸腔积液间皮素对间皮瘤的特异性为100%，在细胞学阴性的积液（n = 105）中阴性预测值为94%。胸腔积液间皮素的个体内可重复性极佳：间皮瘤患者在7天内采集的样本中，平均（±标准差）变化为 - 0.15（±8.41）nM。胸膜固定术后测量结果仍然可靠，且不受细菌存在的影响。
相对于细胞学检查，胸腔积液间皮素具有附加诊断价值。间皮素测量具有可重复性，且不受胸膜炎症过程的影响。
