Clinical Impact and Reliability of Pleural Fluid Mesothelin in Undiagnosed Pleural Effusions
Clinical Impact and Reliability of Pleural Fluid Mesothelin in Undiagnosed Pleural Effusions
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DOI：
10.1164/rccm.200811-1729oc
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发表时间：
2009-09-01
影响因子：
24.7
通讯作者：
Lee, Y. C. Gary
中科院分区：
文献类型：
--
作者：
Davies, Helen E.;Sadler, Ross S.;Lee, Y. C. Gary
血清间皮蛋白是诊断间皮瘤的一种新的生物标志物。间皮瘤患者通常表现为胸腔积液。为了明确胸腔积液中间硫蛋白定量的临床应用价值，我们评估了其在胸腔积液细胞学检查中的附加价值及其在胸膜炎等胸膜炎症过程中的短期重复性和可靠性。目的：评价胸水中间甲内蛋白的诊断作用以及可能影响测定准确性的常见临床因素的作用。方法：采用双抗体夹心ELISA法对4 2 4例胸腔积液和血清标本进行间硫蛋白定量。前瞻性地从167名表现为胸腔积液的患者身上收集液体进行调查。连续胸腔积液样本取自33例需要重复引流的患者。测量和主要结果：间皮瘤患者(n=24)的胸水间皮蛋白浓度显著高于转移性癌(n=67)和良性胸腔积液(n=75)患者：中位数(四分位数范围，第25-75百分位数)分别为40.3(18.3-68.1)、6.1(1.5-13.2nM)和3.7(0.0-12.4)nM，P<；0.0001。间皮蛋白测定在诊断和排除间皮瘤方面优于细胞学检查(敏感度分别为71%和35%；特异度分别为89%和100%；阴性预测值分别为95%和82%)。在细胞学“可疑”的患者中，胸水中的间硫蛋白对间皮瘤的特异性为100%，而在细胞学阴性的积液中(n=105)，其阴性预测值为94%。间皮瘤患者胸腔积液的平均(+/-SD)变异为-0.15(+/-8.41)nM，个体内重复性良好。胸膜固定术后的检测结果仍然可靠，且不受细菌存在的影响。结论：相对于细胞学检查，胸腔积液间皮蛋白具有更高的诊断价值。间硫蛋白测定是可重复性的，不受炎性胸膜过程的影响。
Rationale 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.Objectives: To assess the diagnostic role of pleural fluid mesothelin and the effect of common clinical factors that may influence measurement accuracy.Methods: 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.Measurements and Main Results: 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.Conclusions: Pleural fluid mesothelin provides additional diagnostic value relative to cytological examination. Mesothelin measurements are reproducible and not affected by inflammatory pleural processes.