Fiorelli Alfonso, Ricci Serena, Feola Antonia, Mazzella Antonio, D'Angelo Luigi, Santini Mario, Di Domenico Marina, Di Carlo Angelina
Thoracic Surgery Unit, Second University of Naples, Naples, Italy
Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy.
Interact Cardiovasc Thorac Surg. 2016 Apr;22(4):411-8. doi: 10.1093/icvts/ivv378. Epub 2016 Jan 13.
The aim of the present study was to evaluate the diagnostic accuracy of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in differentiating benign from malignant exudative pleural effusions.
This is a unicentre observational study including 97 consecutive patients with exudative pleural effusions. Metalloproteinase-9, tissue inhibitor of metalloproteinase-1, lactate dehydrogenase, ferritin, carcinoembryonic antigen and carbohydrate antigen 15-3 were measured in pleural effusion and serum by enzyme-linked immunosorbent assay. The activity of metalloproteinase-9 was also evaluated by substrate zymography. The data were correlated with final diagnosis of pleural effusions to evaluate the diagnostic accuracy.
Of the 97 eligible patients, 6 were excluded. Of the 91 patients included in the study, 70 had malignant pleural effusions and 21 had benign pleural effusions. Both in sera and pleural effusions, matrix metalloproteinase-9 (P < 0.0001), tissue inhibitor of metalloproteinase-1 (P < 0.0001) and carcinoembryonic antigen (P < 0.0001) levels were higher in neoplastic patients than in benign group. Zymography analysis showed a most prominent band at a molecular weight of 92 kDa (metalloproteinase-9) whereas a less intense band was observed at 72 kDa (metalloproteinase-2). A significant correlation was found between metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in pleural effusion (P < 0.0001; r = 0.8) and serum (P < 0.03; r = 0.2). Pleural effusion metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed higher value of sensitivity (97 and 91%, respectively) and specificity (90 and 95%, respectively) compared with other standard markers. Serum metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed similar results. Among 70 neoplastic patients, 29 had negative pleural cytology. Of these, 25 presented elevated levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, whereas 4 patients had elevated levels of one of the two markers.
Our results showed that metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 might be valuable markers in differentiating benign from malignant pleural effusions. Their levels are neither influenced by the histology and tumour origin nor by the presence of tumour cells in pleural effusions. Thus, their use in clinical practice could help in the selection of patients needing more invasive procedures, such as thoracoscopic biopsy.
本研究旨在评估基质金属蛋白酶-9和金属蛋白酶组织抑制剂-1在鉴别良性与恶性渗出性胸腔积液中的诊断准确性。
这是一项单中心观察性研究，纳入了97例连续性渗出性胸腔积液患者。采用酶联免疫吸附测定法检测胸腔积液和血清中的基质金属蛋白酶-9、金属蛋白酶组织抑制剂-1、乳酸脱氢酶、铁蛋白、癌胚抗原和糖类抗原15-3。还通过底物凝胶酶谱法评估基质金属蛋白酶-9的活性。将数据与胸腔积液的最终诊断相关联，以评估诊断准确性。
97例符合条件的患者中，6例被排除。在纳入研究的91例患者中，70例为恶性胸腔积液，21例为良性胸腔积液。无论是血清还是胸腔积液中，肿瘤患者的基质金属蛋白酶-9（P<0.0001）、金属蛋白酶组织抑制剂-1（P<0.0001）和癌胚抗原（P<0.0001）水平均高于良性组。凝胶酶谱分析显示，分子量为92 kDa处有一条最明显的条带（基质金属蛋白酶-9），而在72 kDa处观察到一条较弱的条带（基质金属蛋白酶-2）。胸腔积液中基质金属蛋白酶-9与金属蛋白酶组织抑制剂-1水平之间存在显著相关性（P<0.0001；r=0.8），血清中也存在显著相关性（P<0.03；r=0.2）。与其他标准标志物相比，胸腔积液中的基质金属蛋白酶-9和金属蛋白酶组织抑制剂-1水平显示出更高的敏感性（分别为97%和91%）和特异性（分别为90%和95%）。血清中的基质金属蛋白酶-9和金属蛋白酶组织抑制剂-1水平显示出相似的结果。在70例肿瘤患者中，29例胸腔积液细胞学检查为阴性。其中，25例基质金属蛋白酶-9和金属蛋白酶组织抑制剂-1水平升高，而4例患者两种标志物之一水平升高。
我们的结果表明，基质金属蛋白酶-9和金属蛋白酶组织抑制剂-1可能是鉴别良性与恶性胸腔积液的有价值标志物。它们的水平既不受组织学和肿瘤起源的影响，也不受胸腔积液中肿瘤细胞存在与否的影响。因此，在临床实践中使用它们有助于选择需要更具侵入性检查（如胸腔镜活检）的患者。
