Identification of novel markers for the diagnosis of malignant pleural mesothelioma

Our plain-English summary of Identification of novel markers for the diagnosis of malignant pleural mesothelioma, by F. Gueugnon, S. Leclercq, C. Blanquart, et al (The American Journal of Pathology, 2011).

The study

• Authors: F. Gueugnon, S. Leclercq, C. Blanquart, C. Sagan, L. Cellerin, M. Padieu, C. Perigaud, A. Scherpereel, M. Gregoire
• Journal: The American Journal of Pathology
• Published: 2011;178(3):1033-42
• Cited by: 82 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The diagnosis of malignant pleural mesothelioma is difficult, with the most common differential diagnoses being benign pleural diseases and metastatic adenocarcinomas (ADCA). To identify novel markers that would be able to improve diagnostic accuracy, we performed a genome-wide gene expression analysis on tumor cell lines established from pleural effusions (malignant pleural mesothelioma and lung ADCA). This analysis led to the identification of genes encoding novel and pertinent cellular and soluble markers, for which the expression was validated by real-time RT-PCR. Immunohistochemical staining of tumor biopsy specimens with anti-type III collagen antibodies showed positive labeling for mesothelioma cells but not for ADCA cells. Using enzyme-linked immunosorbent assay, we showed that the C-C motif chemokine 2 (CCL2) concentration was significantly higher in pleural effusions from patients with mesothelioma (n = 61) than in subjects with ADCA (n = 25) or with benign pleural effusions (n = 15): median (interquartile range) = 2.99 ng/ml (1.76 to 6.01) vs 0.99 ng/ml (0.51 to 1.83) and 1.47 ng/ml (0.80 to 1.56), respectively, P < 0.0001. Conversely, the galectin-3 concentration was lower in mesothelioma: 11.50 ng/ml (6.73 to 23.53) vs 24.74 ng/ml (20.42 to 70.35) and 17.64 ng/ml (14.81 to 24.68), respectively, P < 0.0001. The areas under the curve for CCL2 were 0.8030 and 0.7716 for the differentiation of mesothelioma from ADCA or benign pleural effusions, respectively. Similarly, the areas under the curve obtained for galectin-3 were 0.7980 and 0.6923, respectively. In conclusion, type III collagen, CCL2, and galectin-3 are promising new diagnostic markers for mesothelioma.

Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

In plain English

This French laboratory study looked for new markers to help tell malignant pleural mesothelioma apart from metastatic adenocarcinoma and from benign pleural disease. The authors first compared gene activity in 17 tumor cell lines grown from the pleural fluid of patients with mesothelioma or lung adenocarcinoma. They found 74 genes more active in mesothelioma cells and nine more active in adenocarcinoma cells. Staining for type III collagen marked tumor cells in 5 mesothelioma biopsies but not in 6 adenocarcinoma biopsies. The authors then measured two proteins in pleural fluid from 101 patients at Laënnec Hospital, St-Herblain (1998 to 2010): 61 with mesothelioma, 25 with metastatic adenocarcinoma and 15 with benign effusions. Median CCL2 was 2.99 ng/ml in mesothelioma, compared with 0.99 ng/ml in adenocarcinoma and 1.47 ng/ml in benign effusions. Median galectin-3 was lower in mesothelioma (11.50 ng/ml) than in adenocarcinoma (24.74 ng/ml). Confirmed asbestos exposure was recorded in 27 of the 61 mesothelioma patients. The authors concluded that these markers may be useful. They noted that the benign group was small and that larger multicenter studies are needed.

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: Laboratory diagnostic marker study. It combined genome-wide gene expression analysis of tumor cell lines grown from pleural effusions, confirmation by real-time RT-PCR, immunohistochemistry on tumor biopsies, and ELISA measurements in pleural fluids.
• Who was studied: Pleural fluid from 101 patients at Laënnec Hospital (St-Herblain, France), collected 1998 to 2010: 61 with malignant pleural mesothelioma, 25 with pleural metastasis of various carcinomas (ADCA group) and 15 with benign pleural effusions. The gene analysis used 17 cancer cell lines (51 samples). Immunohistochemistry used an independent set of 11 tumor biopsies.
• Exposure: This was not a study of asbestos exposure, and no fiber types were given. Patient characteristics list confirmed asbestos exposure in 27 (44.2%) of the mesothelioma group, 3 (12%) of the ADCA group and 4 (26.6%) of the benign effusion group.
• Main results:
  • In the cell lines, 74 genes were overexpressed in mesothelioma cell lines and nine in adenocarcinoma cell lines.
  • Three mesothelioma cell line samples grouped with the adenocarcinoma samples in the gene-expression analysis.
  • Type III collagen (COL3A1) staining in 11 tumor biopsies (5 mesothelioma, 6 adenocarcinoma) showed cytoplasmic staining in 100% of mesothelioma cells.
  • Adenocarcinoma cells did not stain for type III collagen; only the surrounding stroma stained.
  • Median (interquartile range) CCL2 in pleural fluid was 2.99 ng/ml (1.76 to 6.01) in mesothelioma (n 61), 0.99 ng/ml (0.51 to 1.83) in ADCA (n 25) and 1.47 ng/ml (0.80 to 1.56) in benign effusions (n 15). P was less than 0.0001.
  • Median galectin-3 was lower in mesothelioma at 11.50 ng/ml (6.73 to 23.53) than in ADCA at 24.74 ng/ml (20.42 to 70.35).
  • The authors stated galectin-3 may not be useful to distinguish mesothelioma from benign effusions; the benign group median was 17.64 ng/ml (14.81 to 24.68).
  • For distinguishing mesothelioma from ADCA, the area under the ROC curve was 0.8030 (95% CI 0.7061 to 0.8998) for CCL2 and 0.7980 (0.7019 to 0.8942) for galectin-3.
  • At a CCL2 cut-off of 1.79 ng/ml, sensitivity was 76% and specificity 73.8% for mesothelioma versus ADCA.
  • To reach 96% sensitivity with CCL2 (cut-off 3.26 ng/ml), specificity fell to 49.2%.
  • For mesothelioma versus benign effusions, the CCL2 AUC was 0.7716 (0.6429 to 0.9003).
  • For mesothelioma versus benign effusions, the galectin-3 AUC was 0.6923 (reported in the abstract).
• The authors' conclusion: The authors concluded that type III collagen, CCL2 and galectin-3 may be useful, either for staining tumor tissue or for measuring soluble factors in pleural effusions. They called the data promising but said further work is needed.
• Limitations the authors state:
  • The number of benign cases was relatively small (15).
  • The type III collagen staining results need confirmation in more samples, including other tumor types and atypical mesothelial hyperplasia.
  • Not all candidate genes were tested.
  • Further multicenter studies with larger series of patients are needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Adenocarcinoma, Pleural Effusion, Immunohistochemistry, Biopsy, Collagen, Mesothelioma.

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