Clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma

Our plain-English summary of Clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma, by A. Murakami, C. Tabata, R. Tabata, et al (Oncology Letters, 2012).

The study

• Authors: A. Murakami, C. Tabata, R. Tabata, H. Okuwa, T. Nakano
• Journal: Oncology Letters
• Published: 2012;3(3):581-585
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM exhibits a limited response to conventional chemotherapy and radiotherapy. This, early diagnosis of MPM is essential. Malignant tumor progression requires the destruction of the basement membrane, which is constructed from extracellular matrix (ECM) materials. Various types of human tumor cells are reported to produce ECM-degrading proteases that are important in tumor progression. Among this group of proteolytic enzymes, matrix metalloproteinases (MMPs) are thought to be important due to their wide degrading function. We investigated the pleural effusion MMP-3 levels of patients with MPM and compared them with those of a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion. The pleural effusion MMP-3 concentrations of 52 MPM patients and 67 non-MPM patients were measured. The results showed that the MPM patients had significantly higher pleural effusion MMP-3 levels than the population with non-malignant pleuritis. The overall survival of the MPM patients with lower pleural effusion MMP-3 levels was longer than that of patients with higher pleural effusion MMP-3 levels. Our data therefore suggest a clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma.

In plain English

This Japanese hospital study measured an enzyme called MMP-3 in fluid drawn from around the lungs (pleural effusion) of 119 patients seen at Hyogo College of Medicine between 2005 and 2009. Fifty-two had malignant pleural mesothelioma with a documented asbestos exposure history. Thirty-three had non-malignant pleural effusion, 8 of them benign asbestos pleurisy. Thirty-four had lung cancer with malignant effusion and no asbestos exposure. Mean MMP-3 was significantly higher in the mesothelioma group (49.1 ng/ml) than in the non-malignant group (19.8 ng/ml). It was not significantly different from the lung cancer group (33.7 ng/ml). At a cut-off of 50 ng/ml, the test identified 30.8% of mesothelioma patients and correctly excluded 97.0% of non-malignant patients. Among 47 mesothelioma patients followed, survival did not differ significantly between those above and below 50 ng/ml (p=0.51), though the authors described a tendency toward shorter survival with higher levels. The authors concluded that MMP-3 could be a useful diagnostic marker. They noted its low sensitivity and said its value for predicting survival needs further evaluation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Hospital-based biomarker study comparing pleural effusion MMP-3 levels between patient groups, with survival follow-up of the mesothelioma patients
• Who was studied: 119 patients with pleural effusion at the Department of Respiratory Medicine, Hyogo College of Medicine, Japan, 2005 to 2009: 52 with malignant pleural mesothelioma (40 epithelioid, 10 sarcomatoid, 2 biphasic), 33 with non-malignant pleural effusion (including 8 with benign asbestos pleurisy) and 34 with lung cancer with malignant pleural effusion
• Exposure: Asbestos exposure history, verified by interview. Mesothelioma patients had documented exposure, and the lung cancer patients had none. Fiber types, jobs and doses were not reported. MMP-3 in pleural fluid was measured by ELISA.
• Main results:
  • Distinguishing mesothelioma from non-malignant pleural effusion, MMP-3 gave an AUC of 0.651 (95% CI 0.555-0.747). At a cut-off of 50 ng/ml, sensitivity was 30.8% and specificity 97.0%.
  • Mean pleural effusion MMP-3 was significantly higher in mesothelioma patients (49.1 ng/ml, SD 59.1) than in patients with non-malignant pleural effusion (19.8 ng/ml, SD 13.8), p=0.028
  • The mesothelioma group's mean was higher than the lung cancer group's (33.7 ng/ml, SD 22.4), but the difference was not statistically significant (p=0.909)
  • Within the mesothelioma group, MMP-3 levels did not differ significantly by disease stage or by histological type (epithelioid versus non-epithelioid)
  • MMP-3 levels did not differ significantly between benign asbestos pleurisy (14.4 ng/ml, SD 9.0) and benign pleurisy without asbestos exposure (20.3 ng/ml, SD 14.2)
  • At the 50 ng/ml cut-off, compared against the non-malignant group, the positive predictive value was 94.1%
  • At the 50 ng/ml cut-off, the negative predictive value was 47.1%
  • 47 of the 52 mesothelioma patients were followed for up to 1,700 days, and 20 died during follow-up
  • Overall survival did not differ significantly between mesothelioma patients below and above 50 ng/ml (p=0.51). The authors described a tendency for longer survival in the lower-level group.
  • Serum and pleural effusion MMP-2 levels showed no significant differences between mesothelioma and non-mesothelioma patients (data not shown)
• The authors' conclusion: The authors concluded that mesothelioma patients had significantly higher pleural effusion MMP-3 levels than patients with non-malignant pleuritis, including benign asbestos pleurisy, suggesting MMP-3 may be a useful diagnostic marker of mesothelioma
• Limitations the authors state:
  • Sensitivity at the 50 ng/ml cut-off was low (30.8%), so the authors said the test cannot be used to pick out mesothelioma among patients with lower MMP-3 levels
  • The authors stated that the value of MMP-3 for predicting survival needs further evaluation

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Pleural Mesothelioma, Asbestos Exposure, Chemotherapy, Lung Cancer, Overall Survival.

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