UQ Thoracic Research Centre, School of Medicine, The University of Queensland, Queensland, Australia.
BMC Cancer. 2012 Sep 25;12:428. doi: 10.1186/1471-2407-12-428.
The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE.
We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA.
Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively).
Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice.
恶性胸腔积液（MPE）的诊断常常具有临床挑战性，特别是在细胞学检查为阴性时。DNA 完整性指数已被报道为一种恶性肿瘤标志物。本研究旨在评估胸腔积液 DNA 完整性指数在 MPE 诊断中的应用价值。
我们研究了连续入选的 75 例胸腔积液和配对血清样本。通过实时定量 PCR 检测胸腔积液和血清中的 ALU DNA 重复序列[115bp、247bp 和 247bp/115bp 比值（DNA 完整性指数）]。采用 ELISA 法检测胸腔积液和血清中的间皮素水平。
根据临床病理评估，52 例患者为 MPE（包括 16 例间皮瘤），23 例为良性胸腔积液。与良性胸腔积液相比，MPE 患者的胸腔积液 DNA 完整性指数更高（1.2 比 0.8；p<0.001）。细胞学检查诊断 MPE 的敏感性为 55%。如果同时考虑细胞学检查和胸腔积液 DNA 完整性指数，它们在区分良性和恶性胸腔积液方面具有 81%的敏感性和 87%的特异性。在细胞学阴性的胸腔积液（35 例 MPE 和 28 例良性胸腔积液）中，升高的胸腔积液 DNA 完整性指数对检测 MPE 具有 81%的阳性预测值。在检测间皮瘤方面，胸腔积液 DNA 完整性指数的特异性为 90%，与胸腔积液和血清间皮素（分别为 75%）的敏感性相似。
胸腔积液 DNA 完整性指数是一种很有前途的诊断生物标志物，可用于识别 MPE，包括间皮瘤。该生物标志物在细胞学检查为阴性的 MPE 患者中可能特别有用，并可指导进行更具侵袭性的确诊性检测。目前正在进行一项前瞻性验证研究，以验证我们的研究结果，并测试该生物标志物在改变临床实践方面的临床应用价值。
